Directed Evolution of 2'-Fluoro-Modified, RNA-Supported Carbohydrate Clusters That Bind Tightly to HIV Antibody 2G12.

ABSTRACT: Carbohydrate binding proteins (CBPs) are attractive targets in medicine and biology. Multivalency, with several glycans binding to several binding pockets in the CBP, is important for high-affinity interactions. Herein, we describe a novel platform for design of multivalent carbohydrate cluster ligands by directed evolution, in which serum-stable 2'-fluoro modified RNA (F-RNA) backbones evolve to present the glycan in optimal clusters. We have validated this method by the selection of oligomannose (Man₉) glycan clusters from a sequence pool of ∼10¹³ that bind to broadly neutralizing HIV antibody 2G12 with 13 to 36 nM affinities.

SUBMITTER: Redman RL 

PROVIDER: S-EPMC8589008 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature