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https://hdl.handle.net/2440/92371
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Type: | Journal article |
Title: | Macrocyclic protease inhibitors with reduced peptide character |
Author: | Chua, K. Pietsch, M. Zhang, X. Hautmann, S. Chan, H. Bruning, J. Gütschow, M. Abell, A. |
Citation: | Angewandte Chemie International Edition, 2014; 53(30):7828-7831 |
Publisher: | Wiley |
Issue Date: | 2014 |
ISSN: | 1433-7851 1521-3773 |
Statement of Responsibility: | Krystle C. H. Chua, Markus Pietsch, Xiaozhou Zhang, Stephanie Hautmann, Hon Y. Chan, John B. Bruning, Michael Gütschow, and Andrew D. Abell |
Abstract: | There is a real need for simple structures that define a β-strand conformation, a secondary structure that is central to peptide-protein interactions. For example, protease substrates and inhibitors almost universally adopt this geometry on active site binding. A planar pyrrole is used to replace two amino acids of a peptide backbone to generate a simple macrocycle that retains the required geometry for active site binding. The resulting β-strand templates have reduced peptide character and provide potent protease inhibitors with the attachment of an appropriate amino aldehyde to the C-terminus. Picomolar inhibitors of cathepsin L and S are reported and the mode of binding of one example to the model protease chymotrypsin is defined by X-ray crystallography. |
Keywords: | inhibitors; macrocycles; peptidomimetics; proteases; β-strands |
Rights: | © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim |
DOI: | 10.1002/anie.201404301 |
Published version: | http://dx.doi.org/10.1002/anie.201404301 |
Appears in Collections: | Aurora harvest 2 IPAS publications |
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