title: Non-covalent polyvalent ligands by self-assembly of small glycodendrimers: a novel concept for the inhibition of polyvalent carbohydrate-protein interactions in vitro and in vivo.
abstract: Polyvalent carbohydrate-protein interactions occur frequently in biology, particularly in recognition events on cellular membranes. Collectively, they can be much stronger than corresponding monovalent interactions, rendering it difficult to control them with individual small molecules. Artificial macromolecules have been used as polyvalent ligands to inhibit polyvalent processes; however, both reproducible synthesis and appropriate characterization of such complex entities is demanding. Herein, we present an alternative concept avoiding conventional macromolecules. Small glycodendrimers which fulfill single molecule entity criteria self-assemble to form non-covalent nanoparticles. These particles-not the individual molecules-function as polyvalent ligands, efficiently inhibiting polyvalent processes both in vitro and in vivo. The synthesis and characterization of these glycodendrimers is described in detail. Furthermore, we report on the characterization of the non-covalent nanoparticles formed and on their biological evaluation.
authors.affiliation: Novartis Institutes for BioMedical Research, Lichtstrasse 35, 4056 Basel, Switzerland. gebhard.thoma@novartis.com
authors.forename: Gebhard
authors.initials: G
authors.lastname: Thoma
authors.forename: Markus B
authors.initials: MB
authors.lastname: Streiff
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Katopodis
authors.forename: Rudolf O
authors.initials: RO
authors.lastname: Duthaler
authors.forename: Nicolas H
authors.initials: NH
authors.lastname: Voelcker
authors.forename: Claus
authors.initials: C
authors.lastname: Ehrhardt
authors.forename: Christophe
authors.initials: C
authors.lastname: Masson
mesh_terms: D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D019295:Computational Biology; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000378:metabolism*; D006001:Glycoconjugates / Q000138:chemical synthesis / Q000737:chemistry*; D006461:Hemolysis; D006801:Humans; D007075:Immunoglobulin M / Q000737:chemistry / Q000378:metabolism*; D066298:In Vitro Techniques; D008024:Ligands; D008252:Macaca fascicularis; D009682:Magnetic Resonance Spectroscopy; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D036103:Nanotechnology; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000737:chemistry*; D010316:Particle Size; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D013552:Swine
chemical_list: D006001:Glycoconjugates; D007075:Immunoglobulin M; D008024:Ligands; D009844:Oligosaccharides; D012709:Serum Albumin