Pre-equilibrium competitive library screening for tuning inhibitor association rate and specificity toward serine proteases.

ABSTRACT: High structural and sequence similarity within protein families can pose significant challenges to the development of selective inhibitors, especially toward proteolytic enzymes. Such enzymes usually belong to large families of closely similar proteases and may also hydrolyze, with different rates, protein- or peptide-based inhibitors. To address this challenge, we employed a combinatorial yeast surface display library approach complemented with a novel pre-equilibrium, competitive screening strategy for facile assessment of the effects of multiple mutations on inhibitor association rates and binding specificity. As a proof of principle for this combined approach, we utilized this strategy to alter inhibitor/protease association rates and to tailor the selectivity of the amyloid β-protein

SUBMITTER: Cohen I 

PROVIDER: S-EPMC5929103 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature