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Fragment-Based Drug Design Facilitated by Protein-Templated Click Chemistry: Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin.

ABSTRACT: There is an urgent need for the development of efficient methodologies that accelerate drug discovery. We demonstrate that the strategic combination of fragment linking/optimization and protein-templated click chemistry is an efficient and powerful method that accelerates the hit-identification process for the aspartic protease endothiapepsin. The best binder, which inhibits endothiapepsin with an IC50 value of 43??m, represents the first example of triazole-based inhibitors of endothiapepsin. Our strategy could find application on a whole range of drug targets.

SUBMITTER: Mondal M

PROVIDER: S-EPMC5095814 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Fragment-Based Drug Design Facilitated by Protein-Templated Click Chemistry: Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin.

Mondal Milon M Unver M Yagiz MY Pal Asish A Bakker Matthijs M Berrier Stephan P SP Hirsch Anna K H AK

Chemistry (Weinheim an der Bergstrasse, Germany) 20160907 42

There is an urgent need for the development of efficient methodologies that accelerate drug discovery. We demonstrate that the strategic combination of fragment linking/optimization and protein-templated click chemistry is an efficient and powerful method that accelerates the hit-identification process for the aspartic protease endothiapepsin. The best binder, which inhibits endothiapepsin with an IC<sub>50</sub> value of 43 μm, represents the first example of triazole-based inhibitors of endoth ...[more]

PMID: 27604032

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