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

作者：Zhang X; Bruning J B; George J H; Abell A D^*

来源：Organic and Biomolecular Chemistry, 2016, 14(29): 6970-6978.

DOI：10.1039/c6ob01159d

Here we describe an NMR and X-ray crystallography-based characterisation of the mechanism by which a new class of macrocyclic peptidomimetic aldehyde inhibits alpha-chymotrypsin. In particular, a C-13-labelled analogue of the inhibitor was prepared and used in NMR experiments to confirm formation of a hemiacetal intermediate on binding with alpha-chymotrypsin. Analysis of an X-ray crystallographic structure in complex with alpha-chymotrypsin reveals that the backbone adopts a stable beta-strand conformation as per its design. Binding is further stabilised by interaction with the oxyanion hole near the S-1 subsite and multiple hydrogen bonds.

• 出版日期2016