The role of N-terminal heterocycles in hydrogen bonding to α-chymotrypsin

Nicholas C Schumann, John Bruning, Andrew C Marshall, Andrew D Abell

Research output: Contribution to journalArticle

Abstract

A series of dipeptide aldehydes containing different N-terminal heterocycles was prepared and assayed in vitro against α-chymotrypsin to ascertain the importance of the heterocycle in maintaining a β-strand geometry while also providing a hydrogen bond donor equivalent to the backbone amide nitrogen of the surrogate amino acid. The dipeptide containing a pyrrole constraint (10) was the most potent inhibitor, with >30-fold improved activity over dipeptides which lacked a nitrogen hydrogen bond donor (namely thiophene 11, furan 12 and pyridine 13). Molecular docking studies of 10 bound to α-chymotrypsin demonstrates a hydrogen bond between the pyrrole nitrogen donor and the backbone carbonyl of Gly216 located in the S3 pocket which is proposed to be critical for overall binding.

Original languageEnglish
Pages (from-to)396-399
Number of pages4
JournalBioorganic & medicinal chemistry letters
Volume29
Issue number3
DOIs
Publication statusPublished - Feb 2019
Externally publishedYes

Fingerprint Dive into the research topics of 'The role of N-terminal heterocycles in hydrogen bonding to α-chymotrypsin'. Together they form a unique fingerprint.

Cite this