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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.

Authors :
Mondal M
Unver MY
Pal A
Bakker M
Berrier SP
Hirsch AK
Source :
Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2016 Oct 10; Vol. 22 (42), pp. 14826-14830. Date of Electronic Publication: 2016 Sep 07.
Publication Year :
2016

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 IC <subscript>50</subscript> value of 43 μm, represents the first example of triazole-based inhibitors of endothiapepsin. Our strategy could find application on a whole range of drug targets.<br /> (© 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Details

Language :
English
ISSN :
1521-3765
Volume :
22
Issue :
42
Database :
MEDLINE
Journal :
Chemistry (Weinheim an der Bergstrasse, Germany)
Publication Type :
Academic Journal
Accession number :
27604032
Full Text :
https://doi.org/10.1002/chem.201603001