Targeting of the Leishmania mexicana cysteine protease CPB2.8ΔCTE by decorated fused benzo[b]thiophene scaffold

A potent and highly selective anhydride-based inhibitor of Leishmania mexicana cysteine protease CPB2.8ΔCTE (IC 50 = 3.7 μM) was identified. The details of the interaction of the ligand with the enzyme active site were investigated by NMR biomimetic experiments and docking studies. Results of inhibi...

Full description

Saved in:
Bibliographic Details
Published in:RSC advances 2016, Vol.6 (36), p.30628-30635
Main Authors: Scala, A., Micale, N., Piperno, A., Rescifina, A., Schirmeister, T., Kesselring, J., Grassi, G.
Format: Article
Language:English
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A potent and highly selective anhydride-based inhibitor of Leishmania mexicana cysteine protease CPB2.8ΔCTE (IC 50 = 3.7 μM) was identified. The details of the interaction of the ligand with the enzyme active site were investigated by NMR biomimetic experiments and docking studies. Results of inhibition assays, NMR and theoretical studies indicate that the ligand acts initially as a non-covalent inhibitor and later as an irreversible covalent inhibitor by chemoselective attack of CYS 25 thiolate to an anhydride carbonyl.
ISSN:2046-2069
2046-2069
DOI:10.1039/C6RA05557E