Adhesion Inhibition of F1C‐Fimbriated Escherichia coli and Pseudomonas aeruginosa PAK and PAO by Multivalent Carbohydrate Ligands

Abstract

In order to evaluate their inhibition of bacterial adhesion, the carbohydrate sequences GalNAcbeta1-->4Gal and GalNAcbeta1-->4Galbeta1-->4Glc were synthesized. The disaccharide was conjugated to dendrons based on the 3,5-di-(2-aminoethoxy)-benzoic acid branching unit to yield di- and tetravalent versions of these compounds. A divalent compound was also prepared that had significantly longer spacer arms. Relevant monovalent compounds were prepared for comparison. Their anti-adhesion properties against F1C-fimbriated uropathogenic Escherichia coli were evaluated in an ELISA-type assay by using a recombinant strain and also by using Pseudomonas aeruginosa strains PAO and PAK. Adhesion inhibition was observed in all cases, and multivalency effects of up to one order of magnitude were observed. The combination of spacer and multivalency effects led to a 38-fold increase in the potency of a divalent inhibitor with long spacer arms towards the PAO strain when compared with the free carbohydrate.

Enhanced Inhibition of Protein Carbohydrate Interactions by Dendritic Multivalent Glycoligands

“…The same type of dendritic compounds as 16, but now linked to the sequence GalNAcβ1,4Gal, was tested as adhesion inhibitor for the opportunistic pathogen Pseudomonas aeruginosa. Unfortunately multivalency enhancements were less than an order of magnitude (38). More recent developments on P. aeruginosa adhesion have focused on two soluble lectins of this pathogen, LecA and LecB (or PA-IL and PA-IIL), on the surface of the bacterium.…”

Multivalent Vancomycins and Related Antibiotics Against Infectious Diseases

“…These interactions prevail in biological systems, and are just starting to be explored systematically [34][35][36][37][38][39][40][41][42][43][44][45][46]. Scheme 1 illustrates a well-defined multivalent interaction with linear geometry, in which the multivalent interaction is stronger than corresponding monovalent interaction.…”

A facile synthesis of the GalNAcβ1→4Gal target sequence of respiratory pathogens

“…After the addition of additional CH 2 Cl 2 (40 mL), the organic phase was washed with aq NaHCO 3 (satd 2 · 50 mL), water (50 mL) and dried with Na 2 SO 4 . After concentration, product 7 was purified with silica gel column chromatography with 2% MeOH-CH 2 (10). Compound 7 (0.96 g, 1.9 mmol) and 9 (0.87 g, 1.82 mmol) were dissolved in dry CH 2 Cl 2 (2.5 mL) and stirred under argon in the presence of activated crushed 4 Å molecular sieves.…”

“…Liberation of the 4-OH by reductive opening of the benzylidene ring by NaCNBH 3 was followed by NIS promoted glycosylation with donor 9, which was prepared in three steps from D D-(+)-galactosamine hydrochloride in 66% overall yield. 2 This donor, which was also readily made in multigram amounts, contained a Troc protecting group reported to significantly increase donor reactivity in coupling reactions while effecting good b-selectivity as well. 9 The coupling resulted solely in the b-linked-disaccharide 10.…”