Sulphated penta-galloyl glucopyranoside (SPGG) is glycosaminoglycan mimetic allosteric inhibitor of cathepsin G.

ABSTRACT:

Objective

Cathepsin G (CatG) is a cationic serine protease with wide substrate specificity. CatG is reported to play a role in several inflammatory pathologies. Thus, we aimed at identifying a potent and allosteric inhibitor of CatG to be used as a platform in further drug development opportunities.

Methods

Chromogenic substrate hydrolysis assays were used to evaluate the inhibition potency and selectivity of SPGG towards CatG. Salt-dependent studies, Michaelis-Menten kinetics and SDS-PAGE were exploited to decipher the mechanism of CatG inhibition by SPGG. Molecular modelling was also used to identify a plausible binding site.

Key findings

SPGG displayed an inhibition potency of 57 nM against CatG, which was substantially selective over other proteases. SPGG protecte

SUBMITTER: Al-Horani RA 

PROVIDER: S-EPMC9942669 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature