Tuning the preference of thiodigalactoside- and lactosamine-based ligands to galectin-3 over galectin-1.

Inhibitors for galectin-1 and -3 were synthesized from thiodigalactoside and lactosamine by derivatization of the galactose C3. Introduction of 4-phenyl-1H-1,2,3-triazol-1-yl substituents at the thiodigalactoside C3 by CuAAC, targeting arginine-arene interactions, increased the affinity to 13 nM but yielded little selectivity. The bulkier 4-(4-phenoxyphenyl)-1H-1,2,3-triazol-1-yl substituent, however, increased the preference for galectin-3 over galectin-1 to more than 200-fold.

Use of tetravalent galabiose for inhibition of streptococcus suis serotype 2 infection in a mouse model.

Streptococcus suis is an important swine pathogen associated with a variety of infections such as meningitis, arthritis and septicemia. The bacterium is zoonotic and has been found to cause meningitis especially in humans occupationally exposed to infected pigs. Since adhesion is a prerequisite for colonization and subsequent infection, anti-adhesion treatment seems a natural alternative to traditional treatment with antibiotics.

Rapid screening of lectins for multivalency effects with a glycodendrimer microarray.

Multivalency is an important phenomenon in protein-carbohydrate interactions. In order to evaluate glycodendrimers as multivalent inhibitors of carbohydrate binding proteins, we displayed them on a microarray surface. Valencies were varied from 1 to 8, and corrections were made for the valencies so that all surfaces contained the same amount of the sugar ligand.

Detection of pathogenic Streptococcus suis bacteria using magnetic glycoparticles.

Detection of the zoonotic bacterial pathogen Streptococcus suis was achieved using magnetic glycoparticles. The bacteria contain an adhesion protein for the carbohydrate sequence Galalpha1,4Gal. After incubation with various amounts of the pathogen, magnetic concentration and ATP detection, bacterial levels down to 10(5) cfu could be detected.

ITAM-derived phosphopeptide-containing dendrimers as multivalent ligands for Syk tandem SH2 domain.

Spleen tyrosine kinase (Syk) is activated when its tandem SH2 domain (tSH2) binds to a diphosphorylated ITAM motif of e.g. the FcepsilonRI receptor.

Potential scorpionate antibiotics: targeted hydrolysis of lipid II containing model membranes by vancomycin-TACzyme conjugates and modulation of their antibacterial activity by Zn-ions.

The antibiotic vancomycin-that binds lipid II in the bacterial cell membrane-was conjugated to a mono- and tetravalent mimic of the tris-histidine catalytic triad of metalloenzymes. Targeted hydrolysis by the conjugate was observed using model membranes containing lipid II, and in vitro MIC-values of the targeted mimic constructs could be modulated by Zn-ions.

The influence of ligand valency on aggregation mechanisms for inhibiting bacterial toxins.

Divalent and tetravalent analogues of ganglioside GM1 are potent inhibitors of cholera toxin and Escherichia coli heat-labile toxin. However, they show little increase in inherent affinity when compared to the corresponding monovalent carbohydrate ligand. Analytical ultracentrifugation and dynamic light scattering have been used to demonstrate that the multivalent inhibitors induce protein aggregation and the formation of space-filling networks.

Multivalent carbohydrate recognition on a glycodendrimer-functionalized flow-through chip.

Dendrimers were fitted out with up to eight mannose moieties by "click" chemistry. They were subsequently attached to aluminum oxide chips via a spacer that was linked to the dendrimer core; this resulted in a microarray of glycodendrimers. Binding of the glycodendrimers to the fluorescent lectins ConA and GNA was observable in real time.

Synthesis of multivalent Streptococcus suis adhesion inhibitors by enzymatic cleavage of polygalacturonic acid and 'click' conjugation.

A galabiose disaccharide building block was synthesized by an efficient pectinase cleavage of polygalacturonic acid and subsequent chemical functional group transformations. Besides the disaccharide, the corresponding trisaccharide was also obtained and modified. The compounds were subsequently conjugated to dendrimers with up to eight end groups using 'click' chemistry.

Strong inhibition of cholera toxin binding by galactose dendrimers.

Galactose-containing dendrimers with long spacer arms inhibit cholera toxin binding as strongly as the natural ganglioside GM1 oligosaccharide does.