title: Oligomannoside mimetics by glycosylation of 'octopus glycosides' and their investigation as inhibitors of type 1 fimbriae-mediated adhesion of Escherichia coli.
abstract: The glycocalyx of eukaryotic cells is composed of glycoconjugates, which carry highly complex oligosaccharide portions. To elucidate the biological role and function of the glycocalyx in cell-cell communication and cellular adhesion processes, glycomimetics have become targets of glycosciences, which resemble the composition and structural complexity of the glycocalyx constituents. Here, we report about the synthesis of a class of oligosaccharide mimetics of a high-mannose type, which were obtained by mannosylation of spacered mono- and oligosaccharide cores. These carbohydrate-centered cluster mannosides have been targeted as inhibitors of mannose-specific bacterial adhesion, which is mediated by so-called type 1 fimbriae. Their inhibitory potencies were measured by ELISA and compared to methyl mannoside as well as to a series of mannobiosides, and finally to the polysaccharide mannan. The obtained results suggest a new interpretation of the mechanisms of bacterial adhesion according to a macromolecular rather than a multivalency effect.
authors.affiliation: Otto Diels Institute of Organic Chemistry, Christiana Albertina University of Kiel, Otto-Hahn-Platz 4, 24098, Kiel, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Dubber
authors.forename: Oliver
authors.initials: O
authors.lastname: Sperling
authors.forename: Thisbe K
authors.initials: TK
authors.lastname: Lindhorst
mesh_terms: D001422:Bacterial Adhesion / Q000187:drug effects*; D040761:Biomimetic Materials / Q000737:chemistry* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000502:physiology; D010861:Fimbriae, Bacterial / Q000187:drug effects*; D006027:Glycosides / Q000737:chemistry / Q000378:metabolism*; D006031:Glycosylation / Q000187:drug effects; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D006027:Glycosides; D009844:Oligosaccharides; C028569:oligomannoside