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|Title:||Macrocyclic protease inhibitors with reduced peptide character|
|Citation:||Angewandte Chemie International Edition, 2014; 53(30):7828-7831|
|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|
|Appears in Collections:||IPAS publications|
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