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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

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

Redman Richard L RL Krauss Isaac J IJ

Journal of the American Chemical Society 20210607 23

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 oligomanno ...[more]

PMID: 34096703

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