Bioactive Peptides

The unique composition of milk makes this basic foodstuff into an exceptional raw material for the production of new ingredients with desired properties and diverse applications in the food industry. The fractionation of milk is the key in the development of those ingredients and products; hence continuous research and development on this field, especially various levels of fractionation and separation by filtration, have been carried out. This review focuses on the production of milk fractions as well as their particular properties, applications and processes that increase their exploitation. Whey proteins and caseins from the protein fraction are excellent emulsifiers and protein supplements. Besides, they can be chemically or enzymatically modified to obtain bioactive peptides with numerous functional and nutritional properties. In this context, valorization techniques of cheese-whey proteins, by-product of dairy industry that constitutes both economic and environmental problems, are being developed. Phospholipids from the milk fat fraction are powerful emulsifiers and also have exclusive nutraceutical properties. In addition, enzyme modification of milk phospholipids makes it possible to tailor emulsifiers with particular properties. However, several aspects remain to be overcome; those refer to a deeper understanding of the healthy, functional and nutritional properties of these new ingredients that might be barriers for its use and acceptability. Additionally, in this review, alternative applications of milk constituents in the non-food area such as in the manufacture of plastic materials and textile fibers are also introduced. The unmet needs, the cross-fertilization in between various protein domains,the carbon footprint requirements, the environmental necessities, the health and wellness new demand, etc., are dominant factors in the search for innovation approaches; these factors are also outlining the further innovation potential deriving from those “apparent” constrains obliging science and technology to take them into account.

The remarkable growth of therapeutic peptide development in the past decade has led to a large number of market approvals and the market value is expected to hit $25 billion by 2018. This significant market increase is driven by the increasing incidences of metabolic and cardiovascular diseases and technological advancements in peptide synthesis. For this reason, the search for bioactive peptides has also increased exponentially. Many bioactive peptides from food and nonfood sources have shown positive health effects yet, obstacles such as the need to implement efficient and cost-effective strategies for industrial scale production, good manufacturing practices as well as well-designed clinical trials to provide robust evidence for supporting health claims continue to exist. Several other factors such as the possibility of allergenicity, toxicity and the stability of biological functions of the peptides during gastrointestinal digestion would need to be addressed.

Soil samples were collected from different forest areas of Kerala and screened for laccase activity using guaiacol plate assay technique. An increased concentration of guaiacol was used for the isolation of resistant strains. Substrate oxidation studies were carried out and the potent organisms were taken for enzyme production studies. The organisms,
isolated by the screening strategies, were found efficient laccase producers. The potent organisms were identified as Arthrographis sp. and Enterobacter
cloacae. The enzyme production rate of Arthrographis was found to increase logarithmically and a maximum quantity of 53 U/ml was obtained and the bacterial strain, Enterobacter cloacae, gave a maximum laccase activity of 8U/ml. The difference in the pattern of substrate oxidation by laccase from different organisms is paid attention in the study.

Proteomic and peptidomic studies are emerging as an important part of the holistic approach to food science and technology and have been recently applied in the study and production of bioactive peptides. Food-derived bioac-tive peptides are short amino acid chains with a known sequence that may have one or more biological activities. The proteomic and peptidomic approach to bioactive peptide studies includes bioinformatics, chemometric tools and proteomic/peptidomic methods. A proteomic and peptidomic approach applied to the study of bioactive peptides allows optimizing their production and finding peptides of interest and contributes to understand the interaction mechanisms between receptor and bioactive peptides. The objective of this review was to describe recent analytical tools used for studying various aspects of food-derived biopeptides, emphasizing their production at laboratory and industrial scale.

A B S T R A C T The present study has aimed to evaluate the microencapsulation process of the different casein hydrolysates and to assess the physical properties (moisture content, water activity, bulk density, tapped density, solubility and hygroscopicity), antioxidant activities, chemical structure (FTIR), microstructure and bitterness-masking of the spray-dried powders. The microencapsulation process was done using a laboratory spray-dryer and maltodextrin (DE = 18) as the carrier agent. The obtained results indicated the hygroscopicity of the casein hydrolysates was significantly reduced after microencapsulation process (P < 0.05). By evaluating the antioxidant properties, it became clear that the DPPH free radical scavenging activity, ABTS radical scavenging activity, hydroxyl radical scavenging activity, reducing power, Fe 2+ and Cu 2+ chelating activity were maintained as 90.4–98.5%, 77.5–91.6%, 77.2–93.1%, 95.2–99.6%, and 76.7–98.4% after the spray-drying process, respectively. FTIR spectrometry proved the presence of the hydrolysates in the structure of the microcapsules. The scanning electron microscopy images showed the production of hollow particles with a matrix-type structure. In addition, sensory evaluation of the pastilles fortified with microencapsulated and free hydrolysates suggested that the spray-drying has been effective in reducing the bitterness of these compounds.

A b s t r a c t A r t i c l e I n f o This review is a comprehensive survey of unique, unusual, and rare fatty acids incorporated into natural marine and terrestrial peptides obtained from fungi, fungal endophytes, lichenized ascomycetes, basidiomycetes, and actinomycetes. Lots of fungal peptides display important biological activities of interest, which includes antitumor, antibacterial, antimicrobial, antifungal, phototoxic, HIV inhibitory, immunosuppressive properties, and other pharmacological activities. There is no doubt that they are of great importance, especially in medicinal chemistry and/or pharmaceutical application. This review presents structures of more than 150 fatty acids, incorporated into marine and terrestrial fungal lipopeptides.

The present investigation was carried out to determine the possible bioactive components of tuber of Ruellia tuberosa L. (Acanthaceae) using GC-MS analysis. Twenty five compounds were identified. The prevailing compounds in the ethanol extract of tuber of R. tuberosa were Lupeol (68.14%), Stigmasterol (8.89%), á-Sitosterol (3.99%), Sucrose (2.24%), Cholest-5-ene, 3-bromo-, (3á- (2.24%), Octadecane, 2-methyl- (2.10%), Nonadecane, 2-methyl- (1.93%), Eicosane, 2-methyl- (1.79%) Heptacosane (1.43%) and Heptacosane (1.29%).

E l amaranto es una planta dicoƟledónea no gramínea que produce semillas Ɵpo grano, por lo que se considera un pseudocereal. Pertenece a la familia Amaranthaceae, consƟtuida por aproximadamente 70 géneros, de los cuales, el género Amaranthus comprende alrededor de 60 especies, siendo solo tres (Figura 1) las que se culƟvan para la producción de semillas comesƟbles: A. hypochondriacus L. (México), A. cruentus L. (Centroamérica) y A. caudatus L. (Sudamérica, principalmente en Perú y Ecuador).

The world is aging rapidly; thus, the management of elderly health at an advanced age poses a new research challenge. The elderly is vulnerable to not only malnutrition but also hypofunction of all organs and a variety of chronic diseases such as sarcopenia, osteoporosis, gastrointestinal dysfunction, and mental problems. As the major macronutrient, food protein plays an important role in elderly health and well-being. In this chapter, the function of protein and peptide in elderly health as well as their effects on preventing aging-related disease is reviewed.

Bean protein isolate and phaseolin were hydrolysed using pepsin and pancreatin, and the resulting hydrolysates were filtered through a 1 kDa cutoff membrane and fractionated by size exclusion chromatography. Three fractions corresponding to MW 0.7–1.0 kDa, 0.43–0.7 kDa and <0.43 kDa (A1, A2, and A3 for protein isolate fractions, and B1, B2, and B3 for phaseolin fractions) were assayed for antioxidant and metal chelating activity and they were also subjected to amino acid and SDS–PAGE analysis. Fractions A1 and B1 had the highest copper chelating activity (78% and 82%, respectively), while iron chelating activity was the highest in fractions A1 and B3 (36% and 16%, respectively). Fractions A2 and B3 had the highest antioxidant activity as determined by inhibition of reducing power and b-carotene bleaching, while the highest ABTS radical scavenging activity was found in A3 and B3. Thus, fractions coming from the isolate and phaseolin had similar activities except for iron chelation, suggesting that phaseolin is the major contributor to the antioxidant and copper chelating activities of the hydrolysed protein isolate. Crown

Ozone-inducible (OI ) peptides found in plants contain repeated sequences consisting of a hexa-repeat unit (YGH GGG) repeated 8–10 times in tandem, and each unit tightly binds copper. To date, the biochemical roles for OI peptides are not fully understood. Here, we demonstrated that the hexa-repeat unit from OI peptides behaves as metal-binding motif
catalytically active in the superoxide generation. Lastly, possible mechanisms of the reaction and biological consequence of the reactions are discussed by analogy to the action of human prion octarepeat peptides.

A search in a database of potential bioactive short sequences in food proteins reveals that bioactive peptides with a variety of beneficial effects for cardiovascular health are present in the sequence of common bean proteins, including bioactive sequences with antioxidant properties. A protein isolate, the storage protein phaseolin and a lectin extract from Phaseolus vulgaris L. var. Jamapa, were hydrolyzed by treatment with pepsin and pancreatin in order to investigate the possible release of peptides with antioxidant and metal chelating properties. Antioxidant activity was determined in Caco-2 cells exposed to a free radical generator, and iron and copper chelating activities were determined using colorimetric methods. The highest antioxidant activity, 71% inhibition, was found in the hydrolyzed protein isolate. Copper and iron chelating activities were highest in the lectin and phaseolin hydrolysates, 53% and 81%, respectively. Thus, experimental data indicates, as suggested by the database search, that antioxidant peptides are abundant in pepsin-pancreatin hydrolysates, which may represent a valuable health-promoting property in common bean.

The economic evaluation for the production of fruit juice from the Africa star apple otherwise known as 'Agbalumo' in the south western part of Nigeria was evaluated using the NPV (Net Present value) and IRR (Internal Rate of Return) methods assuming a uniform cash flow over a 10-year plant life. Sensitivity analysis was conducted by varying the number of production days (330, 300 and 250 days) at 100% plant capacity and varying the plant capacity (100, 85 and 70%) for a 330-day production schedule. Some components of the operating cost reduced with number of days and plant capacities. The production cost and product cost per unit increased with either plant capacity utilization or the number of days. It was observed that product cost/ 500ml Tetra Pak of Agbalumo juice at 85% and 70% stood at ₦37.48 while payback time/profitability percent had better index at 300 and 250 days compared to 330 days of plant operation. The results further indicated that the plant should not be operated for less than 250 days and plant capacity utilization of 70% in the year. Flexibility in the plant capacity utilization in the range of 70%-85% for 330 days shows a good economic performance as well as result of the NPV and IRR for this operating condition.

This paper shows the potential of dual enzyme approach on antioxidant activity of casein hydrolysates. Casein was hydrolysed using the proteolytic enzymes alcalase, flavourzyme in isolation and in sequential order. Casein hydrolysates were evaluated for the degree of hydrolysis, antioxidant activity, molecular weight distribution patterns and peptide sequence. Casein hydrolysate produced by the sequential hydrolysis of alcalase and fla-vourzyme showed higher degree of hydrolysis and antioxidant activity as compared to hydrolysate obtained by individual enzymes. In size exclusion chromatograph of casein hydrolysate S3, peptides with molecular weight of 0.57 kDa share 12% area in total area of chromatogram which was 10 times higher than that of hydrolysate S1 and nearly half of that of hydrolysate S2. On subjecting to HPLC-TOF-ESI separation potential antioxidant peptides were identified. The peptide sequence VLPVPQ along with potential fragments was identified in hydrolysate S1 and S2 and HPHPHLS along with its potential sequence was identified in hydrolysate S1, S2 and S3. Sequential hydrolysis of casein showed better antioxidant activity and peptide profile in less duration as compared to the casein hydrolysate obtained by individual enzyme. Electronic supplementary material The online version of this article (https://doi.

Bioactive peptides are found in hidden or inactive sequence of amino acids in milk protein and
digestion or enzyme-mediated proteolysis while open interests advanced food processing. Biologically active
peptides, to this day have been demonstrated to be effective as the immune system stimulants, mineral
binders, opioids, antihypertensives, antithrombotic, antimicrobial, anticancer, antioxidant, increase the
absorption of calcium and lovering blood cholesterol level. The importance of bioactive peptides is associated
with effects on human health and the production of new functional foods. Therefore, today attracted the attention of many areas including life sciences, food science and nutrition and health have become supportive
of functional foods or used in pharmaceutical preparations. Besides the known biological effects in vivo
studies, but need to understand more fully the effects of some other, the results obtained from studies
conducted to date have been promising.

Cancer has become a serious concern in public health. Harmful side effects and multidrug resistance of traditional chemotherapy have prompted urgent needs for novel anticancer drugs or therapeutic approaches. Anticancer peptides (ACPs) have become promising molecules for novel anticancer agents because of their unique mechanism and several extraordinary properties. Most α-helical ACPs target the cell membrane, and interactions between ACPs and cell membrane components are believed to be the key factor in the selective killing of cancer cells. In this review, we focus on the exploitation of the structure and function of α-helical ACPs, including the distinction between cancer and normal cells, the proposed anticancer mechanisms, and the influence of physicochemical parameters of α-helical ACPs on the biological activities and selectivity against cancer cells. In addition, the design and modification methods to optimize the cell selectivity of α-helical ACPs are considered. Furthermore, the suitability of ACPs as cancer therapeutics is discussed.

Peptides obtained from three varieties of common beans (Phaseolus vulgaris L.) named plus black (PB), azufrado higuera (AH) and pinto Saltillo (PS) presented antimicrobial, antioxidant and antihypertensive activities. Peptides were obtained from these common beans protein concentrates after treatment with Alcalase® followed by ultrafiltration using 1-, 3- and 10-kDa molecular weight cutoff membranes. Antioxidant activity was determined by the 2,2′-azino-bis (3-etilbenzotiazolin-6-sulfonic) acid method and was expressed as Trolox equivalent antioxidant capacity (TEAC). The highest antioxidant activity (630, 550 and 517 mM TEAC/mg protein) was observed in the group of peptides with a molecular weight lower than 1 kDa (F < 1) from PB, AH and PS bean varieties, respectively. Antibacterial activity was determined as susceptibility test in which ten of twelve bacteria strains showed growth inhibition with the total hydrolysates (TH) and the peptidic fraction 3–10 kDa; subsequently, the minimum inhibitory concentration was determined with the standard microdilution assay in a 96-well plates in which the peptidic fraction F < 1 kDa presented antimicrobial activity against Shigella dysenteriae with the three beans varieties at 0.1, 0.4 and 0.3 mg/mL (for PB, AH and PS, respectively). Additionally to the antimicrobial and antioxidant activities, the TH of the PB and AH bean varieties presented high inhibition of the angiotensin-I-converting enzyme (ACE-I) (IC50 = 4.34 ± 0.29 and 4.82 ± 1.59 μg/mL, respectively). And, when the peptidic fraction F3–10 kDa was tested, the AH variety showed a significant increase in the ACE-I capacity (IC50 = 1.09 ± 0.04 μg/mL). Importantly, this peptidic fraction decreased the systolic blood pressure in a spontaneously hypertensive rat model after 2 h of administration by a single interperitoneally dose.

Winged bean [Psophocarpus tetragonolobus (L.) DC.] seed is a potential underexploited source of vegetable protein due to its high protein content. In the present work, undefatted and defatted winged bean seed hydrolysates, designated as UWBSH and DWBSH, respectively were produced separately by four proteolytic enzymes namely Flavourzyme, Alcalase, Bromelain, and Papain using pH-stat method in a batch reactor. Enzymatic hydrolysis was carried out over a period of 0.5 to 5 h. UWBSH and DWBSH produced were tested for their ACE inhibitory activity in relation to the hydrolysis time and degree of hydrolysis (DH). Maximum ACE inhibitory activity, both for UWBSH and DWBSH, were observed during 3 to 5 h of hydrolysis. Both, UWBSH (DH 91.84 %), and DWSBH (DH 18.72 %), produced by Papain at 5 h hydrolysis, exhibited exceptionally high ACE inhibitory activity with IC 50 value 0.064 and 0.249 mgmL −1 , respectively. Besides, papain-produced UWBSH and DWBSH were further frac-tionated into three fractions based on molecular weight (UWBSH-I, <10 kDa; UWBSH-II, <5 kDa; UWBSH-III, <2 kDa) and (DWBSH-I, <10 kDa; DWBSH-II, <5 kDa; DWBSH-III, <2 kDa). UWBSH-III revealed the highest ACE inhibitory activity (IC 50 0.003 mgmL −1) compared with DWBSH-III (IC 50 0.130 mgmL −1). The results of the present investigation revealed that winged bean seed hydro-lysates can be explored as a potential source of ACE inhibitory peptides suggesting their uses for physiological benefits as well as for other functional food applications. Keywords Undefatted and defatted winged bean seed. Proximate analysis. ACE inhibitory activity. IC 50 value. Degree of hydrolysis. pH-stat titration

In recent years, food protein-derived hydrolysates have received considerable attention
because of their numerous health benefits. Amongst the hydrolysates, those with anti-hypertensive
and anti-oxidative activities are receiving special attention as both activities can play significant
roles in preventing cardiovascular diseases. The present study investigated the angiotensin-I
converting enzyme (ACE) inhibitory and anti-oxidative activities of Actinopyga lecanora (A. lecanora)
hydrolysates, which had been prepared by alcalase, papain, bromelain, flavourzyme, pepsin,
and trypsin under their optimum conditions. The alcalase hydrolysate showed the highest
ACE inhibitory activity (69.8%) after 8 h of hydrolysis while the highest anti-oxidative activities
measured by 2,2-diphenyl 1-1-picrylhydrazyl radical scavenging (DPPH) (56.00%) and ferrous
ion-chelating (FIC) (59.00%) methods were exhibited after 24 h and 8 h of hydrolysis, respectively.
The ACE-inhibitory and anti-oxidative activities displayed dose-dependent trends, and increased
with increasing protein hydrolysate concentrations. Moreover, strong positive correlations between
angiotensin-I converting enzyme (ACE) inhibitory and anti-oxidative activities were also observed.
This study indicates that A. lecanora hydrolysate can be exploited as a source of functional food
owing to its anti-oxidant as well as anti-hypertension functions.

Many proteins have concealed regions in their amino acid sequences that when liberated or exposed by conformational changes can exhibit bioactivity. Two such cryptic bioactive peptides, C2 (with cell adhesive properties) and E1 (with cell adhesive and antioxidant properties) have been isolated from bovine tendon collagen. This investigation deals with the efficacy of these peptides in countering externally generated stress and imparting cyto-protection in mammalian cell systems. The cell survival activity was studied with two cell lines, viz., HeLa and Vero, with varying concentrations of five oxidative stress-generating agents. The activities of the peptides in supporting cell adhesion and countering stress were determined in their coated and dissolved forms. C2 and E1 coated dishes registered 8 times (p<0.01) higher rate of cell survival against oxidative stress than collagen coated dishes. E1 increased stress tolerance levels by >100 times in dissolved form and C2, by 8 times in coated form. The peptides supported faster wound closure than collagen under normal as well as stressed condition. Maximum stress tolerance was observed on C2 coated dishes in the presence of E1 in the medium suggesting that both enhanced cell adhesion and antioxidative activities significantly contribute to the cell survival during stress. The present study emphasizes that collagen peptides, apart from providing a suitable surface for cell adhesion, also confer protection to cells against oxidative stress.Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

In the present study, the alcalase-generated proteolysates obtained after 8 h of proteolysis of stone fish flesh showed the most potent antioxidant activity in terms of DPPH• radical scavenging activity (77.43%, IC50 of 0.5 mg/mL), ABTS• radical scavenging activity (92.73%, IC50 of 0.33 mg/mL) and FRAP value (39.2 mmol/100 mL FeSO4). These proteolysates profiled and characterized as antioxidative peptides. The proteolysates were initially subjected to ultrafiltration using MWCO Spin-X UF. Potent fractions were further characterized based on hydrophobicity using reversed-phase high-performance liquid chromatography (RP-HPLC) and isoelectric point using an OFFGEL isoelectric focusing fractionator. Results indicated that most of the antioxidative peptides found in fractions with a molecular weight (MW) of less than 2 kDa, hydrophilic (hydrophilicity >80%) and basic (pI = 9.7). The final purified fraction with the highest antioxidant activity was selected for peptide identification and sequencing using Q-TOF mass spectrometry. A total of four peptides were identified, from which Peptide 1 (GVSGLHID) showed the highest antioxidant activity and this has potential as a novel bioingredient of nutraceuticals and functional foods to promote human health.

Ageing is widely used in the meat industry to improve tenderness mainly as a result of the breakdown of muscular proteins through the action of endopeptidases during storage time. In addition, meat contains a large pool of other proteolytic enzymes, mainly exopeptidases, which cut from the outer edges of proteins and polypeptides generating a vast array of peptides and free amino acids. Some of these peptides could potentially exert bioactivities of interest for human health. In this study, ACE-inhibitory and anti-oxidant activities during meat ageing in chilled-storage at 4 °C for a period of time of 0, 1, 2, 3 and 4 weeks have been determined. Beef loin steak samples were analysed before and after cooking, and gas-trointestinal digestion was simulated in order to study its effect on the bioactivity. Control and cooked samples showed an increase in the ACE-inhibitory activity from the third week of chilled storage whereas non-significant differences in the antioxidant activity between control and cooked samples were detected during the studied time. After gastrointestinal digestion of samples, there was a significant increment of the ACE-inhibitory and antioxidant activities in comparison with control and cooked samples at all the studied times. As a main conclusion, cooking does not significantly influence the bioactivity detected whereas the in vitro gastrointestinal digestion produces a significant increase in the ACE-inhibitory and antioxidant activities from the first week, probably due to the intense generation of small peptides as a result of the action of gastrointestinal enzymes.

Eight molecules, four peptides (SPs) and four lipopeptides (LPs) derived by rational
design from surfactin, a well‐known secreted biosurfactant from Bacillus subtilis, were
produced employing Fmoc‐based solid‐phase synthesis. These new peptides were
tested to evaluate their potential biosurfactant and biological activities, aiming at
possible applications in industrial, biological, pharmaceutical, and medical use. Five
molecules (SP1, SP2, SP4, LP5, and LP8) presented potential for medical uses, mainly
due to their drug delivery properties as suggested by their synergistic activity with the
antibiotic vancomycin against Staphylococcus aureus. All synthetic peptides showed
low toxicity against Vero cell cultures, in assays of hemolysis, and in different cytotoxicity
assays. In addition, we found that three peptides (SP1, LP6, and LP7) had potential
technological and industrial use because of their emulsifying capacity, low toxicity,
and ability to physically stabilize solutions. These novel molecules retained some
properties of the parental molecule (surfactin, which was originally obtained through
nonribosomal synthesis in Bacillus subtilis) but have the advantage of being linear
peptides, which can be produced at large scales through the use of conventional heterologous
protein expression protocols.

The study of pharmacologically active peptides is central for the understanding of cancer and the development of novel therapeutic approaches. In this context, both qualitative and quantitative determination of bioactive peptides in biological fluids/tissues and their effect on endogenous factors (e.g. hormones) are of great importance. A mass spectrometry-based approach was developed and applied towards the measurement of leuprolide, a peptide drug for the treatment of prostate cancer, in mouse plasma. High-pressure liquid chromatography coupled to a hybrid quadrupole linear ion trap (QqLIT) mass spectrometer, a platform that combines the benefits of triple QqLIT instruments, was employed for the study. Using the described methodology, we established that picomolar concentrations of leuprolide could be measured in mouse plasma (limit of quantification of 0.1 ng/ml). In order to optimize pharmacokinetic properties of analogs of leuprolide, a facile in vivo mouse model was developed and leuprolide concentrations were determined in mouse plasma following intraperitoneal administration. In the same animal model, we demonstrated the versatility of the described MS-based approach by the determination of plasma concentrations of testosterone, an established biomarker for the treatment of prostate cancer. Following dosing with leuprolide, circulating testosterone was increased significantly in comparison to vehicle-treated mice. Finally, in vitro metabolism of leuprolide was evaluated by incubation of leuprolide with mouse kidney membranes, followed by identification of major metabolites by MS. Such studies provide the framework for future evaluation of novel leuprolide analogs with potential therapeutic advantages.

BACKGROUND: Bean seeds are an inexpensive source of protein. Anthracnose disease caused by the fungus Colletotrichum lindemuthianum results in serious losses in common bean (Phaseolus vulgaris L.) crops worldwide, affecting any above-ground plant part, and protein dysfunction, inducing the synthesis of proteins that allow plants to improve their stress tolerance. The aim of this study was to evaluate the use of beans damaged by anthracnose disease as a source of peptides with angiotensin-converting enzyme (ACE-I)-inhibitory activity. RESULTS: Protein concentrates from beans spoiled by anthracnose disease and from regular beans as controls were prepared by alkaline extraction and precipitation at isolelectric pH and hydrolysed using Alcalase 2.4 L. The hydrolysates from spoiled beans had ACE-I-inhibitory activity (IC50 0.0191 mg protein mL-1) and were very similar to those from control beans in terms of ACE-I inhibition, peptide electrophoretic profile and kinetics of hydrolysis. Thus preparation of hydrolysates using beans affected by anthracnose disease would allow for revalorisation of this otherwise wasted product. CONCLUSION: The present results suggest the use of spoiled bean seeds, e.g. anthracnose-damaged beans, as an alternative for the isolation of ACE-I-inhibitory peptides to be further introduced as active ingredients in functional foods. © 2012 Society of Chemical Industry.

A number of biopeptides promoting health benefits have been isolated from food-protein hydrolysates and can be released during enzymatic digestion. Antihypertensive peptides can be part of protein fractions from amaranth grain. The objective of this work was to obtain ACE-inhibitory peptide fractions from
albumin 1 and the globulin of amaranth (Amaranthus  hypochondriacus) grain. Albumin 1 and globulin were hydrolysed with alcalase; hydrolysis was monitored by proteolytic degradation and by ACE-inhibitory activity. The highest ACE-inhibitory activity was 40% and 35% as obtained after 18 and 15 h hydrolysis for albumin 1 and globulin, respectively. Further separation and purification of the ACE-inhibitory eptide fractions were carried out by gel filtration and C18 RP–HPLC. The IC50 was 0.35 ± 0.02 mg/ml for albumin 1 peptide fraction and 0.15 ± 0.03 mg/ml for globulin peptide fraction. Albumin 1 peptide fraction showed an competitive mode of ACE inhibition, whereas the globulin peptide fraction was competitive. The globulin peptide fraction may have one of the most active naturally-occurring ACE-inhibitory peptides.


BACKGROUND: Bean seeds are an inexpensive source of protein. Anthracnose disease caused by the fungus Colletotrichum lindemuthianum results in serious losses in common bean (Phaseolus vulgaris L.) crops worldwide, affecting any above-ground plant part, and protein dysfunction, inducing the synthesis of proteins that allow plants to improve their stress tolerance. The aim of this study was to evaluate the use of beans damaged by anthracnose disease as a source of peptides with angiotensin-converting enzyme (ACE-I)-inhibitory activity.

Conversion of amyloid fibrils by many peptides/proteins involves cytotoxic helix-rich oligomers.
However, their toxicity and biophysical studies remain largely unknown due to their
highly dynamic nature. To address this, we chose two helical peptides (melittin, Mel and
pancreatic polypeptide, PP) and studied their aggregation and toxicity. Mel converted its
random coil structure to oligomeric helical structure upon binding to heparin; however, PP
remained as helix after oligomerization. Interestingly, similar to Parkinson’s associated α-
synuclein (AS) oligomers, Mel and PP also showed tinctorial properties, higher hydrophobic
surface exposure, cellular toxicity and membrane pore formation after oligomerization in the
presence of heparin. We suggest that helix-rich oligomers with exposed hydrophobic surface
are highly cytotoxic to cells irrespective of their disease association. Moreover as Mel
and PP (in the presence of heparin) instantly self-assemble into stable helix-rich amyloidogenic
oligomers; they could be represented as models for understanding the biophysical
and cytotoxic properties of helix-rich intermediates in detail.

This article describes the rational design, synthesis and pharmacological properties of amide -linked cyclic analogues of Luteinizing Hormone -Releasing Hormone (LHRH) with substitutions at positions 1 (Pro), 6 (D-Leu/D-Trp), 9 (Aze) and 10 (BABA/Acp). These LHRH analogues fulfil the conformational requirements that are known in the literature (bend in the 5 -8 segment) to be essential for receptor recognition and activation.

dairy model protein) and Maltodextrin was assessed on spray drying process of honey. The obtained results revealed that no powder will be produced in drying process of honey without using supplements, while using protein in spray drying process (as low as 10%), will increase the efficiency up to 50%. Comparing to that, reaching a similar efficiency will need large amount of Maltodextrin (up to 100% w/w based on dry weight of honey). The mechanism of action of proteins has been proven by other scientists using physical property tests, powder production efficiency and glass transition temperature (Tg). Recent study showed that preferential migration of protein to the surface of droplets/particles, which reduces adhesive behavior (stickiness) between particles and dryer wall by the increase in the surface protein coverage of the particles. The mechanism of Maltodextrin to decrease the stickiness is due to the increase in the overall Tg of the honey powders.

Novel catalytic peptides highly active in conversion of hydrogen peroxide to superoxide are newly designed and proposed as novel probes for assessing the cellular protein phosphorylation/dephosphorylation events possibly available for future clinical applications. One of model peptide was invented by fusing the copper-binding catalytic peptide and Erk1/2 MAP kinase kinase substrate peptide. In order to demonstrate that this type of probes is phosphorylation-sensitive, preliminary data was obtained with non-phosphorylated and phosphorylated peptides at two phosphorylation sites, namely, threonine and tyrosine residues. As expected, model phosphorylations effectively lowered the catalytic activity of the peptide. This is the first implication that phosphorylation-controllable enzyme mimics could be artificially invented. In addition, the author propose a possible application of this type of peptides as the tools or components for constructing a simplified in vitro signaling system processing the phosphorylation signals into the oxidative signals possibly affecting the fate of the living cells.

In this study, a potent angiotensin-converting enzyme
(ACE)-inhibitory activity was found in a commercial
kefir made from caprine milk. The low molecular
mass peptides released from caseins during fermentation
were mainly responsible for this activity. Sixteen
peptides were identified by HPLC-tandem mass spectrometry.
Two of these peptides, with sequences
PYVRYL and LVYPFTGPIPN, showed potent ACE-inhibitory
properties. The impact of gastrointestinal digestion
on ACE-inhibitory activity of kefir peptides was
also evaluated. Some of these peptides were resistant
to the incubation with pepsin followed by hydrolysis
with Corolase PP. The ACE-inhibitory activity after
simulated digestion was similar to or slightly lower
than unhydrolyzed peptides, except for peptide β-casein
f(47-52) (DKIHPF), which exhibited an activity 8 times
greater after hydrolysis.

The extensive use of antibiotics to treat human or animal infections is the cause of an alarming increase in antibiotic resistance among Gram-negative, Gram-positive and fungal pathogens. Therefore, the search continues for new antibiotics that are active in vivo, are fast acting and broad-spectrum, do not induce bacterial resistance and have limited side effects. Synthetic congeners of natural antimicrobial peptides are good candidates. One component of host defence at mucosal surfaces seems to be epithelial derived anti-microbial peptides (AMP). This review summarises the diversity of anti-microbial peptides and their role in gastro-intestinal diseases.

Collagen, a major structural protein of the ECM, is known for its high cell adherence capacity. This study was conducted to identify regions in collagen that harbour such bioactivity. Collagen from tendon was hydrolysed and the peptides fractionated using ion-exchange chromatography (IEC). Isolated peptide fractions were coated onto disposable dishes and screened for cell adherence and proliferative abilities. Active IEC fractions were further purified by chromatography, and two peptides, C2 and E1 with cell adhesion ability, were isolated. A cell adhesion assay done with different amounts of C2 coated onto disposable dishes revealed the maximum adhesion to be 94.6%, compared with 80% for collagen coated dishes and an optimum peptide coating density of 0.507 nmoles per cm 2 area of the dish. Growth of cells on C2, collagen, and E1 revealed a similar pattern and a reduction in the doubling time compared with cells grown on uncoated dishes. C2 had a mass of 2.046 kDa with 22 residues, and sequence analysis revealed a higher percentage occurrence of hydrophilic residues compared with other regions in collagen. Docking studies revealed GDDGEA in C2 as the probable site of interaction with integrins ␣2␤1 and ␣1␤1, and stability studies proved C2 to be mostly protease-resistant.

Background
In the past, many methods have been developed for peptide tertiary structure prediction but they are limited to peptides having natural amino acids. This study describes a method PEPstrMOD, which is an updated version of PEPstr, developed specifically for predicting the structure of peptides containing natural and non-natural/modified residues.

Results
PEPstrMOD integrates Forcefield_NCAA and Forcefield_PTM force field libraries to handle 147 non-natural residues and 32 types of post-translational modifications respectively by performing molecular dynamics using AMBER. AMBER was also used to handle other modifications like peptide cyclization, use of D-amino acids and capping of terminal residues. In addition, GROMACS was used to implement 210 non-natural side-chains in peptides using SwissSideChain force field library. We evaluated the performance of PEPstrMOD on three datasets generated from Protein Data Bank; i) ModPep dataset contains 501 non-natural peptides, ii) ModPep16, a subset of ModPep, and iii) CyclicPep contains 34 cyclic peptides. We achieved backbone Root Mean Square Deviation between the actual and predicted structure of peptides in the range of 3.81–4.05 Å.

Conclusions
In summary, the method PEPstrMOD has been developed that predicts the structure of modified peptide from the sequence/structure given as input. We validated the PEPstrMOD application using a dataset of peptides having non-natural/modified residues. PEPstrMOD offers unique advantages that allow the users to predict the structures of peptides having i) natural residues, ii) non-naturally modified residues, iii) terminal modifications, iv) post-translational modifications, v) D-amino acids, and also allows extended simulation of predicted peptides. This will help the researchers to have prior structural information of modified peptides to further design the peptides for desired therapeutic property. PEPstrMOD is freely available at http://osddlinux.osdd.net/raghava/pepstrmod/

Temporin-1Tl (TL) is a 13-residue frog antimicrobial peptide (AMP) exhibiting potent antimicrobial and anti-inflammatory activity. To develop novel AMP with improved anti-inflammatory activity and antimicrobial selectivity, we designed and synthesized a series of TL analogs by substituting Trp, Arg and Lys at selected positions. Except for Escherichia coli and Staphylococcus epidermidis, all TL analogs exhibited retained or increased antimicrobial activity against seven bacterial strains including three methicillin-resistant Staphylococcus aureus strains compared with TL. TL-1 and TL-4 showed a little increase in antimicrobial selectivity, while TL-2 and TL-3 displayed slightly decreased antimicrobial selectivity because of their about twofold increased hemolytic activity. All TL analogs demonstrated greatly increased anti-inflammatory activity, evident by their higher inhibition of the production tumor necrosis factor-α (TNF-α) and nitric oxide and the mRNA expression of inducible nitric oxide synthase and TNF-α in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells, compared with TL. Taken together, the peptide anti-inflammatory activity is as follows: TL-2 ≈ TL-3 ≈ TL-4 > TL-1 > TL. In addition, LPS binding ability of the peptides corresponded with their anti-inflammatory activity. These results apparently suggest that the anti-inflammatory activity of TL analogs is associated with the direct binding ability between these peptides and LPS. Collectively, our designed TL analogs possess improved anti-inflammatory activity and retain antimicrobial activity without a significant increase in hemolysis. Therefore, it is evident that our TL analogs constitute promising candidates for the development of peptide therapeutics for gram-negative bacterial infection.

Aim: Sheep milk-born bioactive peptides have been found to exhibit various physiological activities. The present work was designed with the aim to evaluate the effect of boiling on antidiabetic property of peptides derived from sheep milk caseinate on hydrolysis with three different proteases. Materials and Methods: In this investigation, casein prepared from raw and boiled sheep milk was hydrolyzed by three commercially available proteases (trypsin, pepsin, and chymotrypsin). These hydrolysates collected at different hydrolysis times (60, 120, 160, and 240 min) were assayed for their antidiabetic activity. Results: Among the three different enzyme hydrolysates, casein treated with chymotrypsin shows the highest antidiabetic activity among other enzymes. While the antidiabetic effect of raw milk-derived casein hydrolysates always exceeds than effect shown by boiled milk casein hydrolysates. Conclusion: The result obtained hence shows that the effect of boiling on the properties of bioactive peptides released during different enzyme digestion depends largely on the enzymatic formulation used and treatment conditions. Chymotrypsin treatment of raw casein yields peptides with maximum antidiabetic activity as compared to pepsin and trypsin. Moreover, the peptides produced after enzymatic treatment of boiled casein show reduced antidiabetic properties. Therefore, enzymatically treated raw milk casein hydrolysates may be used as effective nutritional supplements for diabetic patients, as it causes a significant inhibition of α-amylase activity.

The stone fish is an under-utilized sea cucumber with many nutritional and ethno-medicinal values. This study aimed to establish the conditions for its optimum hydrolysis with bromelain to generate angiotensin I-converting enzyme (ACE)-inhibitory hydrolysates. Response surface methodology (RSM) based on a central composite design was used to model and optimize the degree of hydrolysis (DH) and ACE-inhibitory activity. Process conditions including pH (4–7), temperature (40–70 • C), enzyme/substrate (E/S) ratio (0.5%–2%) and time (30–360 min) were used. A pH of 7.0, temperature of 40 • C, E/S ratio of 2% and time of 240 min were determined using a response surface model as the optimum levels to obtain the maximum ACE-inhibitory activity of 84.26% at 44.59% degree of hydrolysis. Hence, RSM can serve as an effective approach in the design of experiments to improve the antihypertensive effect of stone fish hydrolysates, which can thus be used as a value-added ingredient for various applications in the functional foods industries.

The study of pharmacologically active peptides is central for the understanding of cancer and the development of novel therapeutic approaches. In this context, both qualitative and quantitative determination of bioactive peptides in biological fluids/tissues and their effect on endogenous factors (e.g. hormones) are of great importance. A mass spectrometry-based approach was developed and applied towards the measurement of leuprolide, a peptide drug for the treatment of prostate cancer, in mouse plasma. High-pressure liquid chromatography coupled to a hybrid quadrupole linear ion trap (QqLIT) mass spectrometer, a platform that combines the benefits of triple QqLIT instruments, was employed for the study. Using the described methodology, we established that picomolar concentrations of leuprolide could be measured in mouse plasma (limit of quantification of 0.1 ng/ml). In order to optimize pharmacokinetic properties of analogs of leuprolide, a facile in vivo mouse model was developed and leuprolide concentrations were determined in mouse plasma following intraperitoneal administration. In the same animal model, we demonstrated the versatility of the described MS-based approach by the determination of plasma concentrations of testosterone, an established biomarker for the treatment of prostate cancer. Following dosing with leuprolide, circulating testosterone was increased significantly in comparison to vehicle-treated mice. Finally, in vitro metabolism of leuprolide was evaluated by incubation of leuprolide with mouse kidney membranes, followed by identification of major metabolites by MS. Such studies provide the framework for future evaluation of novel leuprolide analogs with potential therapeutic advantages.

Previously, generation of superoxide anion (O2 •-) catalyzed by Cu-binding peptides derived from human prion protein (model sequence for helical Cu-binding motif VNITKQHTVTTTT was most active) in the presence of catecholamines and related aromatic monoamines such as phenylethylamine and tyramine, has been reported [Kawano, T., Int J Biol Sci 2007; 3: 57-63]. The peptide sequence (corresponding to helix 2) tested here is known as threonine-rich neurotoxic peptide. In the present article, the redox behaviors of aromatic monoamines, 20 amino acids and prion-derived tyrosine-rich peptide sequences were compared as putative targets of the oxidative reactions mediated with the threonine-rich prion-peptide. For detection of O2 •-, an O2 •-specific chemiluminescence probe, Cypridina luciferin analog was used. We found that an aromatic amino acid, tyrosine (structurally similar to tyramine) behaves as one of the best substrates for the O2 •-generating reaction (conversion from hydrogen peroxide) catalyzed by Cu-bound prion helical peptide. Data suggested that phenolic moiety is required to be an active substrate while the presence of neither carboxyl group nor amino group was necessarily required. In addition to the action of free tyrosine, effect of two tyrosine-rich peptide sequences YYR and DYEDRYYRENMHR found in human prion corresponding to the tyrosine-rich region was tested as putative sub-strates for the threonine-rich neurotoxic peptide. YYR motif (found twice in the Y-rich region) showed 2-to 3-fold higher activity compared to free tyrosine. Comparison of Y-rich sequence consisted of 13 amino acids and its Y-to-F substitution mutant sequence revealed that the tyrosine-residues on Y-rich peptide derived from prion may contribute to the higher production of O2 •-. These data suggest that the tyrosine residues on prion molecules could be additional targets of the prion-mediated reactions through intra-or inter-molecular interactions. Lastly, possible mechanism of O2 •-generation and the impacts of such self-redox events on the conformational changes in prion are discussed.

Hydroxyapatite (HA) biomaterials and allograft bone are common alternatives to autogenous grafts, however these materials lack the strong osteoinductive potential of autologous bone. Previous studies have established that polyglutamate domains, which bind selectively to HA, can be engineered onto bioactive peptides as a mechanism for coupling osteoinductive signals onto HA and allograft. In the current investigation, we adapted the polyglutamate approach to tailor delivery of a model collagen-derived peptide, DGEA, by manipulating the number of glutamates in the HA binding domain. Specifically, DGEA was modified with diglutamate (E2-DGEA), tetraglutamate (E4-DGEA) or heptaglutamate (E7-DGEA), and it was found that initial peptide binding to HA and allograft was significantly enhanced as the number of glutamates increased. We also determined that the rate of release of polyglutamate-DGEA from substrates over a 5-day interval increased proportionally as the number of glutamate residues was decreased. Additionally, we tuned the peptide release rate by creating mixtures of E2-DGEA, E4-DGEA and E7-DGEA, and observed that release kinetics of the mixtures were distinct from pure solutions of each respective peptide. These collective results suggest that variable length polyglutamate domains provide an effective mechanism for controlled delivery of osteoregenerative peptides on HA-containing bone graft materials.

The traditional methods for mining foods for bioactive peptides are tedious and long. Similar to the drug industry, the length of time to identify and deliver a commercial health ingredient that reduces disease symptoms can take anything between 5 to 10 years. Reducing this time and effort is crucial in order to create new commercially viable products with clear and important health benefits. In the past few years, bioinformatics, the science that brings together fast computational biology, and efficient genome mining, is appearing as the long awaited solution to this problem. By quickly mining food genomes for characteristics of certain food therapeutic ingredients, researchers can potentially find new ones in a matter of a few weeks. Yet, surprisingly, very little success has been achieved so far using bioinformatics in mining for food bioactives. The absence of food specific bioinformatic mining tools, the slow integration of both experimental mining and bioinformatics, and the important difference between different experimental platforms are some of the reasons for the slow progress of bioinformatics in the field of functional food and more specifically in bioactive peptide discovery. In this paper I discuss some methods that could be easily translated, using a rational peptide bioinformatics design, to food bioactive peptide mining. I highlight the need for an integrated food peptide database. I also discuss how to better integrate experimental work with bioinformatics in order to improve the mining of food for bioactive peptides, therefore achieving a higher success rates.

The current study was carried out for testing the inhibitory spectrum of the metabolic extract of Saccharomyces boulardii yeast against (26) bacterial isolates. The metabolic extract of Saccharomyces boulardii yeast was obtained after growth in YEPG medium and centrifuged. The broad inhibitory spectrum of yeast extract against Gram-positive bacteria and Gram-negative bacteria assay by liquid medium method and solid medium method. The highest inhibition of Enterobacter spp. and B. cereus in the solid medium were (37) mm and (35) mm respectively when adding the inhibitory substances at (100 μL) concentration while the inhibition ratio percentage in the liquid medium was (74.2%) and (72.1%) respectively for both bacteria. Less inhibition diameter for bacteria was E. coli 6 which reaches (18) mm. after adding (100μl) concentrations, while the percentage of inhibition in the liquid medium was (26.7%).

SATPdb (http://crdd.osdd.net/raghava/satpdb/) is a database of structurally annotated therapeutic peptides, curated from 22 public domain peptide databases/datasets including 9 of our own. The current version holds 19192 unique experimentally validated therapeutic peptide sequences having length between 2 and 50 amino acids. It covers peptides having natural, non-natural and modified residues. These peptides were systematically grouped into 10 categories based on their major function or therapeutic property like 1099 anticancer, 10585 antimicrobial, 1642 drug delivery and 1698 antihypertensive peptides. We assigned or annotated structure of these therapeutic peptides using structural databases (Protein Data Bank) and state-of-the-art structure prediction methods like I-TASSER, HHsearch and PEPstrMOD. In addition, SATPdb facilitates users in performing various tasks that include: (i) structure and sequence similarity search, (ii) peptide browsing based on their function and properties, (iii) identification of moonlighting peptides and (iv) searching of peptides having desired structure and therapeutic activities. We hope this database will be useful for researchers working in the field of peptide-based therapeutics.

Cardiovascular function is affected by many mechanisms, including the autonomic system, the kallikrein-kinin system (KKS), the reninangiotensin system (RAS) and the endothelin system. The function of these systems seems to be fairly well preserved throughout the vertebrate scale, but evolution required several adaptations. Snakes are particularly interesting for studies related to the cardiovascular function because of their elongated shape, their wide variation in size and length, and because they had to adapt to extremely different habitats and gravitational influences. To keep the normal cardiovascular control the snakes developed anatomical and functional adaptations and interesting structural peculiarities are found in their autonomic, KKS, RAS and endothelin systems. Our laboratory has characterized some biochemical, pharmacological and physiological properties of these systems in South American snakes. This review compares the components and function of these systems in snakes and other vertebrates, and focuses on differences found in snakes, related with receptor or ligand structure and/or function in autonomic system, RAS and KKS, absence of components in KKS and the intriguing identity between a venom and a plasma component in the endothelin system.

To examine its antidiabetic potential in fluoride (F) intoxicated rats, the
anti-diabetic drug glibenclamide was administered for 4 weeks to diabetic rats and to
diabetic rats exposed to 100 mg NaF/L in the drinking water. In the F treated rats there
was a significant reduction in plasma glucose, plasma and hepatic total lipids,
cholesterol, triglycerides and plasma low-density lipoproteins (LDL), VLDLcholesterol,
and atherogenic index accompanied by significant increases in HDLcholesterol,
FRAP (ferric reducing ability of plasma) and protein content.
Furthermore, significant decreases in SGOT (serum glutamate oxaloacetate
transaminase), SGPT (serum glutamate pyruvate transaminase), alkaline and acid
phosphatase (ALP and ACP), and glucose-6-phosphatase (G-6-Pase) were observed
in these F-treated animals. In addition, administration of the drug decreased hepatic
and renal lipid peroxidation with a concomitant increase in total ascorbic acid (TAA),
superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase
(GPX), and FRAP levels in the F-treated animals. It is proposed that glibenclamide
acts at two levels: (i) at pancreatic islets for increased release of insulin from
surviving β cells, (ii) at the target sites, e.g., hepatic tissue to improve glucose uptake
leading to an improvement in the activities of hepatic and renal TAA, SOD, GSH, GPX,
and reduction in lipid peroxidation. Glibenclamide may therefore be useful for
treatment of diabetes in F endemic areas

Milchwissenschaft 66 (4) 2011 371 CLA is easily oxidized because of its conjugated double bonds, and such oxidization can be prevented by adjusting the O 2 concentration within the reaction system. It has been reported by two laboratories that the CLA production by washed cells of Lactobacillus can be enhanced under micro-aerobic conditions . In addition, our results were consistent with the notion that oxygen can promote oxidative metabolism (23).

toxicity. Improved delivery has the potential to address these challenges. Here, we engineered nanomaterials for antibacte-rial activity employing two strategies to improve delivery which have not yet been explored for treatment of lung infections. First, we screened a library of bifunctional peptides that can localize to bacterial membranes and deliver a toxic payload that can specifically kill Pseudomonas aeruginosa over off-target host cells. Second, we protected the peptide cargo in biodegradable porous silicon nanoparticles (pSiNPs) to delay and extend the release after lung delivery. Antibiotic delivery via pSiNPs has yet to be established for treatment of lung infections. [1,2] Together, these elements combined to form an anti-infective nano-material that we applied to a P. aeruginosa lung infection model (Figure 1A). We found the anti-infective nanomaterial significantly decreased bacterial numbers and improved survival in a mouse model of lung infection. In P. aeruginosa, two concentric membrane structures studded with efflux pumps surround the degradative periplasmic compartment, [3] creating a formidable barrier for antibacterial agents. We hypothesized that peptides could offer a means to specifically localize to bacteria, either by ligand-mediated binding and/ or other physical interaction with membranes. Peptides are There is an urgent need for new materials to treat bacterial infections. In order to improve antibacterial delivery, an anti-infective nanomaterial is developed that utilizes two strategies for localization: i) a biodegradable nanopar-ticle carrier to localize therapeutics within the tissue, and ii) a novel tandem peptide cargo to localize payload to bacterial membranes. First, a library of antibacterial peptides is screened that combines a membrane-localizing pep-tide with a toxic peptide cargo and discovers a tandem peptide that displays synergy between the two domains and is able to kill Pseudomonas aeruginosa at sub-micromolar concentrations. To apply this material to the lung, the tandem peptide is loaded into porous silicon nanoparticles (pSiNPs). Charged peptide payloads are loaded into the pores of the pSiNP at ≈30% mass loading and ≈90% loading efficiency using phosphonate surface chemistry. When delivered to the lungs of mice, this anti-infective nanomaterial exhibits improved safety profiles over free peptides. Moreover, treatment of a lung infection of P. aeruginosa results in a large reduction in bacterial numbers and markedly improves survival compared to untreated mice. Collectively, this study presents the selection of a bifunctional peptide-based anti-infective agent and its delivery via biodegradable nanoparticles for application to an animal model of lung infection. A global threat in the fight against pathogenic bacteria has emerged with the rising incidence of antibiotic resistance combined with the paucity of new antibacterial agents entering the clinic. Two major obstacles facing the development of new antibiotics are poor drug penetration into bacteria and off-target