Papers by Didier Zurwerra
Crystal structure of tubulin-stathmin-TTL-Epothilone A complex
Crystal structure of tubulin-stathmin-TTL complex
ChemInform Abstract: Synthesis and Stability of Boratriazaroles
ChemInform, May 1, 2015
CCDC 980712: Experimental Crystal Structure Determination
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Crystal structure of tubulin-stathmin-TTL complex
Crystal structure of tubulin-stathmin-TTL-Epothilone A complex
ChemInform Abstract: 6π/10π-Electrocyclization of Ketene-iminium Salts for the Synthesis of Substituted Naphthylamines
ChemInform, Sep 4, 2014
An intramolecular 6π/10π-electrocyclization from ketene-iminium salts was developed for the prepa... more An intramolecular 6π/10π-electrocyclization from ketene-iminium salts was developed for the preparation of naphthylamines. Various substituents on the nitrogen, on the aromatic ring, and on the olefin were studied. Tricyclic skeletons were obtained in few steps and good overall yields. The electrocyclization of ketene-iminium salts has been computationally explored by means of DFT calculations and their activation barriers were compared to the parent triene as well as the corresponding dienyl allenes and dienyl ketenes. Electrocyclizations for ketene-iminium salts were shown to be highly exergonic and have much smaller barriers to activation.
Zampanolide (I) and (+)-dactylolide (II) are structurally related polyketidebased macrolides that... more Zampanolide (I) and (+)-dactylolide (II) are structurally related polyketidebased macrolides that were isolated from two taxonomically different, geographically widely separated sponge species. Surprisingly, the absolute stereochemistry for the macrolactone core structure in I is opposite to that found in II (Figure ).
Synthesis of (−)-Dactylolide and 13-Desmethylene-(−)-dactylolide and Their Effects on Tubulin
Organic Letters, 2010
An efficient new synthesis has been elaborated for non-natural (-)-dactylolide ((-)-2) and its 13... more An efficient new synthesis has been elaborated for non-natural (-)-dactylolide ((-)-2) and its 13-desmethylene analogue 4, employing a HWE-based macrocyclization approach with beta-keto-phosphonate/aldehyde 19 and the respective 13-desmethylene derivative as the key intermediates. Both (-)-2 and 4 as well as the corresponding C20 alcohols inhibit human cancer cell proliferation with IC(50) values in the sub-micromolar range and induce the polymerization of tubulin in vitro.
Chemistry - A European Journal, 2012
Scheme 1. Retrosynthesis of (À)-zampanolide (1) and (À)-dactylolide (ent-2). Only key disconnecti... more Scheme 1. Retrosynthesis of (À)-zampanolide (1) and (À)-dactylolide (ent-2). Only key disconnections are highlighted explicitly. PG = protecting group; protecting groups may vary independently. Scheme 2. Retrosynthesis of building block I-2. PG= protecting group. Scheme 3. a) NaAlH 2 (OCH 2 CH 2 OMe) 2 , Et 2 O, 0 8C, then EtOAc, then I 2
Angewandte Chemie International Edition, 2010
Chemistry & Biology, 2012
Zampanolide and its less active analog dactylolide compete with paclitaxel for binding to microtu... more Zampanolide and its less active analog dactylolide compete with paclitaxel for binding to microtubules and represent a new class of microtubule-stabilizing agent (MSA). Mass spectrometry demonstrated that the mechanism of action of both compounds involved covalent binding to β-tubulin at residues N228 and H229 in the taxane site of the microtubule. Alkylation of N228 and H229 was also detected in α,β-tubulin dimers. However, unlike cyclostreptin, the other known MSA that alkylates β-tubulin, zampanolide was a strong MSA. Modeling the structure of the adducts, using the NMR-derived dactylolide conformation, indicated that the stabilizing activity of zampanolide is likely due to interactions with the Mloop. Our results strongly support the existence of the luminal taxane site of microtubules in tubulin dimers and that microtubule nucleation induction by MSAs may proceed through an allosteric mechanism. Highlights-Zampanolide covalently binds to the luminal paclitaxel site at -tubulin N228 and H229.-Labeling occurs in both tubulin dimers and microtubules.-Bound zampanolide models indicate interaction with the M-loop at the paclitaxel site.-Microtubule nucleation may proceed both through matchmaking and allosteric mechanisms.
ChemInform Abstract: Synthesis and Stability of Boratriazaroles
ChemInform, 2015
Synthesis and Stability of Boratriazaroles
Organic Letters, 2015
We describe the synthesis and stability analysis of novel boratriazaroles that can be viewed as b... more We describe the synthesis and stability analysis of novel boratriazaroles that can be viewed as bioisosteres of imidazoles or pyrazoles. These heterocycles could conveniently be obtained by condensing a boronic acid and amidrazone 1 in various solvents. A detailed stability analysis of selected compounds at different pH values as a function of time led to the identification of steric hindrance around the boron atom as a key element for stabilization.
Chemicals Inducing Seed Germination and Early Seedling Development
CHIMIA International Journal for Chemistry, 2014
Seed germination and early seedling development are essential events in the plant life cycle that... more Seed germination and early seedling development are essential events in the plant life cycle that are controlled largely by the interplay and cross-talk between several plant hormones. Recently, major progress has been achieved in the elucidation at the molecular level of the signalling of these phytohormones. In this review, we summarise the data for the most promising classes of compounds, which could find potential agronomic applications for promoting seed germination and early seedling development even under abiotic stress conditions. Structural modifications of plant hormones are required to improve their biological performance and their specificity to allow commercial application.
Tetrahedron Letters, 2014
Science, 2013
Microtubule-stabilizing agents (MSAs) are efficacious chemotherapeutic drugs widely used for the ... more Microtubule-stabilizing agents (MSAs) are efficacious chemotherapeutic drugs widely used for the treatment of cancer. Despite the importance of MSAs for medical applications and basic research, their molecular mechanisms of action on tubulin and microtubules remain elusive. We determined high-resolution crystal structures of αβ-tubulin in complex with two unrelated MSAs, zampanolide and epothilone A. Both compounds were bound to the taxane pocket of β-tubulin and used their respective side chains to induce structuring of the M-loop into a short helix. Because the M-loop establishes lateral tubulin contacts in microtubules, these findings explain how taxane-site MSAs promote microtubule assembly and stability. Further, our results offer fundamental structural insights into the control mechanisms of microtubule dynamics.
Simplified strigolactams as potent analogues of strigolactones for the seed germination induction of Orobanche cumana Wallr
Pest management science, Jan 4, 2016
Strigolactones play an important role in the rhizosphere as signaling molecules stimulating the s... more Strigolactones play an important role in the rhizosphere as signaling molecules stimulating the seed germination of parasitic weed seeds and hyphal branching of arbuscular micorrhiza and also act as hormones in plant roots and shoots. Strigolactone derivatives e.g. strigolactams could be used as suicidal germination inducers in the absence of a host crop for the decontamination of land infested with parasitic weed seeds. We report the stereoselective synthesis of novel strigolactams together with some of their critical physicochemical properties such as water solubility, hydrolytic stability, as well as their short soil persistence. In addition, we show that such strigolactams are potent germination stimulants of O. cumana parasitic weed seeds and do not affect the seed germination and the root growth of sunflower. The novel strigolactam derivatives described here compare favorably with the corresponding GR-28 strigolactones in term of biological activity and physicochemical propert...
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Papers by Didier Zurwerra