Bayón Carlos, He Ning, Deir-Kaspar Mario, Blasco Pilar, André Sabine, Gabius Hans-Joachim, Rumbero Ángel, Jiménez-Barbero Jesús, Fessner Wolf-Dieter, Hernáiz María J
Department of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy, Complutense University, Plaza RamónyCajaL s/n, 28040, Madrid, Spain.
Department of Organic Chemistry and Biochemistry, Technische Universität Darmstadt, A, larich-Weiss-Strasse 4, 64287, Darmstadt, Germany.
Chemistry. 2017 Jan 31;23(7):1623-1633. doi: 10.1002/chem.201604550. Epub 2016 Dec 30.
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.
