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.
Carbohydrate-oligonucleotide conjugates and glycodendrimers were synthesized utilizing a DNA synthesizer. The synthesis of multivalent glycoconjugates on solid-phase allows custom tailoring of their structure to the requirements of biological assays within hours, as opposed to traditional approaches that require weeks or months of work in the laboratory. Therefore it will become much easier to investigate carbohydrate-protein interactions and optimize for objectives such as the receptor-mediated targeting of antisense oligonucleotides.
Pentaerythritol derivatives were used as core molecules for the synthesis of two cluster α-D-mannosides, which were designed as oligomannoside mimetics. The problem of glycosyl orthoester formation, which frequently occurs in oligo-mannosylations, was solved. The clusters were tested for their
Synthetic glycoclusters have gained substantial attention as mimetics of multivalent glycoconjugates. For their proposed glycobiological applications, it is advantageous to incorporate a functionalized tether into the clusters, which allows coupling to solid supports and other molecules such as reporter groups or even bioactive molecules. We herein report the use of carbohydrates as oligofunctional scaffolds for the synthesis of tethered cluster mannosides. Glycocluster 11 was prepared following two different pathways, starting either from glucose or the nonreducing disaccharide trehalose. The oligo alcohols 5 and 14 served as acceptors in the subsequent oligo-mannosylation reaction, in which three main problems were overcome: (i) incomplete glycosylation, (ii) cleavage of the core-glycoside, and (iii) ortho ester formation. Optimum conditions for the glycosylation were identified utilizing an advanced MALDI-TOF protocol.
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