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Direct Enzymatic Branch‐End Extension of Glycocluster‐Presented Glycans: An Effective Strategy for Programming Glycan Bioactivity
Author(s) -
Bayón Carlos,
He Ning,
DeirKaspar Mario,
Blasco Pilar,
André Sabine,
Gabius HansJoachim,
Rumbero Ángel,
JiménezBarbero Jesús,
Fessner WolfDieter,
Hernáiz María J.
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201604550
Subject(s) - glycan , chemistry , biochemistry , moiety , sialic acid , enzyme , neuraminic acid , computational biology , new horizons , peptidomimetic , combinatorial chemistry , stereochemistry , glycoprotein , biology , peptide , engineering , spacecraft , aerospace engineering
The sequence of a glycan and its topology of presentation team up to determine the specificity and selectivity of recognition by saccharide receptors (lectins). Structure–activity analysis would be furthered if the glycan part of a glycocluster could be efficiently elaborated in situ while keeping all other parameters constant. By using a bacterial α2,6‐sialyltransferase and a small library of bi‐ to tetravalent glycoclusters, we illustrate the complete conversion of scaffold‐presented lactoside units into two different sialylated ligands based on N ‐acetyl/glycolyl‐neuraminic acid incorporation. We assess the ensuing effect on their bioactivity for a plant toxin, and present an analysis of the noncovalent substrate binding contacts that the added sialic acid moiety makes to the lectin. Enzymatic diversification of a scaffold‐presented glycan can thus be brought to completion in situ, offering a versatile perspective for rational glycocluster engineering.