Cathepsin B Inhibitors: Combining Dipeptide Nitriles with an Occluding Loop Recognition Element by Click Chemistry
Authors:
- 12 January 2016
- journal article
- research article
- Published by American Chemical Society (ACS) in ACS Medicinal Chemistry Letters
- Vol. 7 (3) , 211-216
Abstract
An active site mapping of human cathepsin B with dipeptide nitrile inhibitors was performed for a combinatorial approach by introducing several points of diversity and stepwise optimizing the inhibitor structure. To address the occluding loop of cathepsin B by a carboxylate moiety, click chemistry to generate linker-connected molecules was applied. Inhibitor 17 exhibited Ki values of 41.3 nM, 27.3 nM, or 19.2 nM, depending on the substrate and pH of the assay. Kinetic data were discussed with respect to the conformational selection and induced fit models.Keywords
Funding Information
- Gender Equality Center, Bonn-Rhein-Sieg University
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