biostudies-literatureJordan CStudienstiftung des Deutschen VolkesWestf?lische Wilhelms-Universit?t M?nsterGottfried Wilhelm Leibniz Universit?t HannoverEuropean Research CouncilDeutsche ForschungsgemeinschaftFonds der Chemischen IndustrieEidgen?ssische Technische Hochschule Z?rich1481-1489https://www.ebi.ac.uk/biostudies/studies/S-EPMC11363330biostudies-literatureUnknown10(8)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 <i>Vibrio cholerae</i>: 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 hydACS central scienceProbing the Origin of Affinity in the GM1-Cholera Toxin Complex through Site-Selective Editing with Fluorine.PMC1136333010100232681894995145937 19-2Teschers CSPape FJordan CBussmann KHayashi TKohnke JAufiero MLobbert AAxer AGilmour RBergander KCampbell EFan JSiebold KGossert ADfalseProbing the Origin of Affinity in the GM1-Cholera Toxin Complex through Site-Selective Editing with Fluorine.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 <i>Vibrio cholerae</i>: 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 hyd2024-01-01T00:00:00Z2024 Aug2026-06-01T16:15:33.884Z2025-04-06T13:44:35.022ZS-EPMC113633303922070610.1021/acscentsci.4c00622