Repurposing the McoTI-II Rigid Molecular Scaffold in to Inhibitor of 'Papain Superfamily' Cysteine Proteases.

ABSTRACT: Clan C1A or 'papain superfamily' cysteine proteases are key players in many important physiological processes and diseases in most living systems. Novel approaches towards the development of their inhibitors can open new avenues in translational medicine. Here, we report a novel design of a re-engineered chimera inhibitor Mco-cysteine protease inhibitor (CPI) to inhibit the activity of C1A cysteine proteases. This was accomplished by grafting the cystatin first hairpin loop conserved motif (QVVAG) onto loop 1 of the ultrastable cyclic peptide scaffold McoTI-II. The recombinantly expressed Mco-CPI protein was able to bind with micromolar affinity to papain and showed remarkable thermostability owing to the formation of multi-disulphide bonds. Using an in silico approach based on homology mo

SUBMITTER: Mishra M 

PROVIDER: S-EPMC7822474 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature