Bacteria use long proteinaceous appendages, called fimbriae or pili, to adhere to the surfaces of their host cells. Widely distributed among the Enterobacteriacae are type 1 fimbriae that mediate mannose-specific bacterial adhesion through the lectin FimH, located at the fimbrial tips. It is possible to design synthetic mannosides such that they show high affinity for FimH and can thus inhibit mannose-specific bacterial adhesion in a competitive manner. It has been found that mannosidic squaric acid monoamides serve especially well as inhibitors of type 1 fimbriae-mediated bacterial adhesion, but it has remained unclear whether this effect is due to specific inhibition of the bacterial lectin FimH or to unspecific bioconjugation between the lectin's carbohydrate binding site and a squaric acid monoamide. A bioconjugation reaction would result in a covalently crosslinked squaric acid diamide. Here it is shown that covalent inhibition of FimH by mannosidic squaric acid derivatives is very unlikely and that compounds of this type serve rather as excellent specific candidates for low-molecular-weight inhibitors of bacterial adhesion. This has been verified by testing the properties of glycosidic squaric acid monoamides in diamide formation, by two different adhesion assays with a series of selected control compounds, and by molecular docking studies that further support the results obtained in the bioassays.

To promote understanding of sugar configuration in a supramolecular context, glycomicelles were compared and a “trinity projection” of glycosides proposed.

The synthesis of amide‐linked glycomimetics is of interest in the glycosciences as they represent a typical linkage in biologically important glycoconjugates. We have addressed the synthesis of three types of N‐glycosyl amide architectures, which were targeted using Staudinger ligation. This facile method has allowed us to synthesize a collection of N‐glycosyloctanamides, N‐glycosyloxyethyl amino acids and multivalent glycoclusters. The last two classes represent molecules that can be used as building blocks in solid‐phase peptide synthesis for the preparation of multivalent glycoconjugates. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)