Genetically-encoded fragment-based discovery of glycopeptide ligands for DC-SIGN |
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Authors: | Simon Ng Nicholas James Bennett Jessica Schulze Nan Gao Christoph Rademacher Ratmir Derda |
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Institution: | 1. Department of Chemistry, University of Alberta, Edmonton, AB T6G 2G2, Canada;2. Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam 14424, Germany |
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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. |
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Keywords: | Peptide phage display Glycopeptides DC-SIGN |
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