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Issue 29, 2016
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A mechanistic study on the inhibition of α-chymotrypsin by a macrocyclic peptidomimetic aldehyde

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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

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Publication details

The article was received on 27 May 2016, accepted on 23 Jun 2016 and first published on 23 Jun 2016


Article type: Paper
DOI: 10.1039/C6OB01159D
Citation: Org. Biomol. Chem., 2016,14, 6970-6978
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    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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