Probing the Origin of Affinity in the GM1-Cholera Toxin Complex through Site-Selective Editing with Fluorine.

ABSTRACT: Carbohydrates regulate an inimitable spectrum of biological functions, yet successfully leveraging this therapeutic avenue continues to be frustrated by low affinities with glycan-specific proteins. A conspicuous exception is the interaction of monosialotetrahexosylganglioside (GM1) with the carbohydrate-recognition domain of cholera toxin from Vibrio cholerae: this is one of the strongest protein-carbohydrate interactions known. To establish the importance of a long-discussed key hydrogen bond between C2 of the terminal galactose of GM1 and the B subunit pentamer of cholera toxin (CTB₅), the total synthesis of a selectively fluorinated GM1 epitope was conducted in 19 steps. This process of molecular editing (O^δ-H → F^δ-) strategically deletes the hyd

SUBMITTER: Jordan C 

PROVIDER: S-EPMC11363330 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature