title: The Impact of Heteromultivalency in Lectin Recognition and Glycosidase Inhibition: An Integrated Mechanistic Study.
abstract: The vision of multivalency as a strategy limited to achieve affinity enhancements between a protein receptor and its putative sugar ligand (glycotope) has proven too simplistic. On the one hand, binding of a glycotope in a dense glycocalix-like construct to a lectin partner has been shown to be sensitive to the presence of a third sugar entity (heterocluster effect). On the other hand, several carbohydrate processing enzymes (glycosidases and glycosyltransferases) have been found to be also responsive to multivalent presentations of binding partners (multivalent enzyme inhibition), a phenomenon first discovered for iminosugar-type inhibitory species (inhitopes) and recently demonstrated for multivalent carbohydrate constructs. By assessing a series of homo- and heteroclusters combining α-d-glucopyranosyl-related glycotopes and inhitopes, it was shown that multivalency and heteromultivalency govern both kinds of events, allowing for activation, deactivation or enhancement of specific recognition phenomena towards a spectrum of lectin and glycosidase partners in a multimodal manner. This unified scenario originates from the ability of (hetero)multivalent architectures to trigger glycosidase binding modes that are reminiscent of those harnessed by lectins, which should be considered when profiling the biological activity of multivalent architectures.
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, University of Sevilla, c/ Profesor García González 1, 41012, Sevilla, Spain.
authors.forename: M Isabel
authors.identifier: http://orcid.org/0000-0003-4273-3010
authors.initials: MI
authors.lastname: García-Moreno
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, University of Sevilla, c/ Profesor García González 1, 41012, Sevilla, Spain.
authors.forename: Fernando
authors.identifier: http://orcid.org/0000-0003-0781-0105
authors.initials: F
authors.lastname: Ortega-Caballero
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, University of Sevilla, c/ Profesor García González 1, 41012, Sevilla, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Rísquez-Cuadro
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, University of Sevilla, c/ Profesor García González 1, 41012, Sevilla, Spain.
authors.forename: Carmen
authors.identifier: http://orcid.org/0000-0002-7676-7721
authors.initials: C
authors.lastname: Ortiz Mellet
authors.affiliation: Instituto de Investigaciones Químicas (IIQ), CSIC-University of Sevilla, Avda. Americo Vespucio 49, 41092, Sevilla, Spain.
authors.forename: José M
authors.identifier: http://orcid.org/0000-0002-6827-0387
authors.initials: JM
authors.lastname: García Fernández
mesh_terms: D017485:1-Deoxynojirimycin / Q000737:chemistry / Q000378:metabolism; D001667:Binding, Competitive; D003208:Concanavalin A / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006735:Horseradish Peroxidase / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D037102:Lectins / Q000737:chemistry / Q000378:metabolism*; D019887:Peanut Agglutinin / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D037102:Lectins; D019887:Peanut Agglutinin; D047392:beta-Cyclodextrins; D003208:Concanavalin A; D017485:1-Deoxynojirimycin; D006735:Horseradish Peroxidase; D006026:Glycoside Hydrolases; C031215:betadex
keywords: carbohydrates; glycomimetics; heteromultivalency; inhibitors; sp2-iminosugars