Dr. Kolb has more than 10 years experience in structure-based drug discovery and combinatorial chemistry. Based on a medicinal chemistry approach, he has developed non-carbohydrate inhibitors for a family of carbohydrate receptors, called 'Selectins' (21,40,41, 34). In collaboration with Professor Barry Sharpless (TSRI), he has developed the click chemistry approach to drug discovery (39,42,44), which comprises a set of heteroatom-bond forming reactions that approach perfection, by virtue of having a high driving force, being reliable, selective, modular and easy to perform. His group has made close to 200,000 individual compounds for screening. Azapeptide Library Design and Production. The azapeptide library shown in Scheme 1, made up of compounds that combine a metal-binding hydroxamate group and a substrate mimic, was designed using computational tools for assessing the drug-like nature of compounds and their likelihood of binding to BoNT B based on the X-ray crystal structure recently published by the Stevens laboratory (30) Analogous computational studies are currently being performed for BoNT A and E, whose crystal structures have recently become available (3, 72).
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