Constrained Combinatorial Libraries of Gp2 Proteins Enhance Discovery of PD-L1 Binders.

ABSTRACT: Engineered protein ligands are used for molecular therapy, diagnostics, and industrial biotechnology. The Gp2 domain is a 45-amino acid scaffold that has been evolved for specific, high-affinity binding to multiple targets by diversification of two solvent-exposed loops. Inspired by sitewise enrichment of select amino acids, including cysteine pairs, in earlier Gp2 discovery campaigns, we hypothesized that the breadth and efficiency of de novo Gp2 discovery will be aided by sitewise amino acid constraint within combinatorial library design. We systematically constructed eight libraries and comparatively evaluated their efficacy for binder discovery via yeast display against a panel of targets. Conservation of a cysteine pair at the termini of the first diversified paratope loop increased b

SUBMITTER: Kruziki MA 

PROVIDER: S-EPMC6051759 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature