title: Direct Enzymatic Branch-End Extension of Glycocluster-Presented Glycans: An Effective Strategy for Programming Glycan Bioactivity.
abstract: 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.
authors.affiliation: Department of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy, Complutense University, Plaza RamónyCajaL s/n, 28040, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Bayón
authors.affiliation: Department of Organic Chemistry and Biochemistry, Technische Universität Darmstadt, A, larich-Weiss-Strasse 4, 64287, Darmstadt, Germany.
authors.forename: Ning
authors.initials: N
authors.lastname: He
authors.affiliation: Department of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy, Complutense University, Plaza RamónyCajaL s/n, 28040, Madrid, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Deir-Kaspar
authors.affiliation: Departamento de Ciencia de Proteínas, CIB-CSIC, C/Ramiro denMaeztu 9, 28040, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Blasco
authors.affiliation: Institut für Physiologische Chemie, Tierärztliche Fakultät, Ludwig-Maximilians-Universität München, Veterinärstrasse 13, 80539, München, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: André
authors.affiliation: Institut für Physiologische Chemie, Tierärztliche Fakultät, Ludwig-Maximilians-Universität München, Veterinärstrasse 13, 80539, München, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Gabius
authors.affiliation: Department of Organic Chemistry, Faculty of Science, Autonoma University of Madrid, Spain.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Rumbero
authors.affiliation: Departamento de Ciencia de Proteínas, CIB-CSIC, C/Ramiro denMaeztu 9, 28040, Madrid, Spain.|Ikerbasque, Basque Foundation for Science, Maria Diaz de Haro 13, 48009, Bilbao, Spain.|Department of Organic Chemistry II, Faculty of Science & Technology, University of the Basque Country, 48940, Leioa, Bizkaia, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Jiménez-Barbero
authors.affiliation: Department of Organic Chemistry and Biochemistry, Technische Universität Darmstadt, A, larich-Weiss-Strasse 4, 64287, Darmstadt, Germany.
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Fessner
authors.affiliation: Department of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy, Complutense University, Plaza RamónyCajaL s/n, 28040, Madrid, Spain.
authors.forename: María J
authors.initials: MJ
authors.lastname: Hernáiz
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D001665:Binding Sites; D007700:Kinetics; D037102:Lectins / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D062105:Molecular Docking Simulation; D009438:Neuraminic Acids / Q000737:chemistry / Q000378:metabolism; D011134:Polysaccharides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012799:Sialyltransferases / Q000378:metabolism; D020349:Surface Plasmon Resonance
chemical_list: D001426:Bacterial Proteins; D037102:Lectins; D008024:Ligands; D009438:Neuraminic Acids; D011134:Polysaccharides; D012799:Sialyltransferases
keywords: carbohydrates; dendrimers; enzyme catalysis; glycoconjugates; molecular recognition