Issue 29, 2016

A mechanistic study on the inhibition of α-chymotrypsin by a macrocyclic peptidomimetic aldehyde

Abstract

Here we describe an NMR and X-ray crystallography-based characterisation of the mechanism by which a new class of macrocyclic peptidomimetic aldehyde inhibits α-chymotrypsin. In particular, a 13C-labelled analogue of the inhibitor was prepared and used in NMR experiments to confirm formation of a hemiacetal intermediate on binding with α-chymotrypsin. Analysis of an X-ray crystallographic structure in complex with α-chymotrypsin reveals that the backbone adopts a stable β-strand conformation as per its design. Binding is further stabilised by interaction with the oxyanion hole near the S1 subsite and multiple hydrogen bonds.

Graphical abstract: A mechanistic study on the inhibition of α-chymotrypsin by a macrocyclic peptidomimetic aldehyde

Supplementary files

Article information

Article type
Paper
Submitted
27 May 2016
Accepted
23 Jun 2016
First published
23 Jun 2016

Org. Biomol. Chem., 2016,14, 6970-6978

Author version available

A mechanistic study on the inhibition of α-chymotrypsin by a macrocyclic peptidomimetic aldehyde

X. Zhang, J. B. Bruning, J. H. George and A. D. Abell, Org. Biomol. Chem., 2016, 14, 6970 DOI: 10.1039/C6OB01159D

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