Genetically-encoded fragment-based discovery of glycopeptide ligands for DC-SIGN. Issue 19 (15th October 2018)

• Record Type: Journal Article
• Authors: Ng, Simon; Bennett, Nicholas James; Schulze, Jessica; Gao, Nan; Rademacher, Christoph; Derda, Ratmir
• Is Part Of: Bioorganic & medicinal chemistry. Volume 26:Issue 19(2018)
• Page Start: 5368
• Page End: 5377
• Publication Date: 2018-10-15
• Subjects: Peptide phage display -- Glycopeptides -- DC-SIGN; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2018.08.036
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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 10 8 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.