Structure and Energetics of Ligand-Fluorine Interactions with Galectin-3 Backbone and Side-Chain Amides: Insight into Solvation Effects and Multipolar Interactions.

ABSTRACT: Multipolar fluorine-amide interactions with backbone and side-chain amides have been described as important for protein-ligand interactions and have been used to improve the potency of synthetic inhibitors. In this study, fluorine interactions within a well-defined binding pocket on galectin-3 were investigated systematically using phenyltriazolyl-thiogalactosides fluorinated singly or multiply at various positions on the phenyl ring. X-ray structures of the C-terminal domain of galectin-3 in complex with eight of these ligands revealed potential orthogonal fluorine-amide interactions with backbone amides and one with a side-chain amide. The two interactions involving main-chain amides seem to have a strong influence on affinity as determined by fluorescence anisotropy. In contrast, the in

SUBMITTER: Kumar R 

PROVIDER: S-EPMC6772088 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature