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ID: ALA4265996

Journal: Bioorg Med Chem

Title: Genetically-encoded fragment-based discovery of glycopeptide ligands for DC-SIGN.

Authors: Ng S, Bennett NJ, Schulze J, Gao N, Rademacher C, Derda R.

Abstract: We have employed genetically-encoded fragment-based discovery to identify novel glycopeptides with affinity for the dendritic cell receptor DC-SIGN. Starting from libraries of 108 mannose-conjugated peptides, we identified glycopeptides that exhibited up to a 650-fold increase in multivalent binding affinity for DC-SIGN, which is also preserved in cells. Monovalently, our most potent glycopeptides have a similar potency to a Man3 oligosaccharide, representing a 15-fold increase in activity compared to mannose. These compounds represent the first examples of glycopeptide ligands that target the CRD of DC-SIGN. The natural framework of glycopeptide conjugates and the simplicity of orthogonal conjugation to make these glycopeptides anticipates a promising future for development of DC-SIGN-targeting moieties.

CiteXplore: 30344001

DOI: 10.1016/j.bmc.2018.08.036