Genetically-encoded fragment-based discovery of glycopeptide ligands for DC-SIGN.
Bioorg Med Chem
; 26(19): 5368-5377, 2018 10 15.
Article
em En
| MEDLINE
| ID: mdl-30344001
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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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Glicopeptídeos
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Moléculas de Adesão Celular
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Receptores de Superfície Celular
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Lectinas Tipo C
Idioma:
En
Revista:
Bioorg Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Canadá