title: Multivalent Carbohydrate-Lectin Interactions: How Synthetic Chemistry Enables Insights into Nanometric Recognition.
abstract: Glycan recognition by sugar receptors (lectins) is intimately involved in many aspects of cell physiology. However, the factors explaining the exquisite selectivity of their functional pairing are not yet fully understood. Studies toward this aim will also help appraise the potential for lectin-directed drug design. With the network of adhesion/growth-regulatory galectins as therapeutic targets, the strategy to recruit synthetic chemistry to systematically elucidate structure-activity relationships is outlined, from monovalent compounds to glyco-clusters and glycodendrimers to biomimetic surfaces. The versatility of the synthetic procedures enables to take examining structural and spatial parameters, alone and in combination, to its limits, for example with the aim to produce inhibitors for distinct galectin(s) that exhibit minimal reactivity to other members of this group. Shaping spatial architectures similar to glycoconjugate aggregates, microdomains or vesicles provides attractive tools to disclose the often still hidden significance of nanometric aspects of the different modes of lectin design (sequence divergence at the lectin site, differences of spatial type of lectin-site presentation). Of note, testing the effectors alone or in combination simulating (patho)physiological conditions, is sure to bring about new insights into the cooperation between lectins and the regulation of their activity.
authors.affiliation: Pharmaqam and Nanoqam, Department of Chemistry, University du Québec à Montréal, P. O. Box 8888, Succ. Centre-Ville, Montréal, QC H3C 3P8, Canada. roy.rene@uqam.ca.
authors.forename: René
authors.initials: R
authors.lastname: Roy
authors.affiliation: School of Chemistry, National University of Ireland Galway, University Road, Galway, Ireland. paul.v.murphy@nuigalway.ie.
authors.forename: Paul V
authors.initials: PV
authors.lastname: Murphy
authors.affiliation: Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University Munich, Veterinärstr. 13, München 80539, Germany. gabius@tiph.vetmed.uni-muenchen.de.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Gabius
mesh_terms: D002241:Carbohydrates / Q000737:chemistry*; D050091:Dendrimers / Q000737:chemistry; D037161:Galectins / Q000737:chemistry* / Q000378:metabolism; D006023:Glycoproteins / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D011134:Polysaccharides / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D002241:Carbohydrates; D050091:Dendrimers; D037161:Galectins; D006023:Glycoproteins; D011134:Polysaccharides
keywords: agglutinin; galectin; glycocluster; glycodendrimer; glycophane; glycoprotein; liposomes; oligosaccharides; sugar code