Oligomannoside mimetics by glycosylation of 'octopus glycosides' and their investigation as inhibitors of type 1 fimbriae-mediated adhesion of Escherichia coli.
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.
Dubber
Michael
M
Otto Diels Institute of Organic Chemistry, Christiana Albertina University of Kiel, Otto-Hahn-Platz 4, 24098, Kiel, Germany.
Sperling
Oliver
O
Lindhorst
Thisbe K
TK
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*
D006027:Glycosides; D009844:Oligosaccharides; C028569:oligomannoside