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Published on: February 7, 2025
Complex of sialoadhesin with a glycopeptide ligand
Jens T Bukrinsky1, Phaedria M St Hilaire, Morten Meldal
1Department of Chemistry, The Carlsberg Laboratory, Gamle Carlsberg Vej 10, DK-2500 Valby, Denmark.
Abstract:
Sialoadhesin is a sialic acid-binding immunoglobulin-like lectin (Siglec), expressed on subsets of macrophages. It is a model system for Siglec receptor-mediated cell surface interactions through binding of sialylated glycoconjugates. The N-terminal sialoadhesin domain can mediate sialic acid-binding on its own. The structure of this domain has been determined in complex with a sialic acid-containing heptapeptide, (Ala-Gly-His-Thr(Neu5Ac)-Trp-Gly-His). The affinity of sialoadhesin for this ligand is four times higher than the affinity for the natural linkage 2,3'-sialyllactose. The structure of the glycopeptide complex suggests strategies for ligand optimization and provides possible explanations for the observed differences in specificities among the Siglecs.
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