title: 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.
authors.affiliation: Department of Medicinal Chemistry, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P. O. Box 80082, 3508 TB Utrecht, The Netherlands.
authors.forename: Reshma
authors.initials: R
authors.lastname: Autar
authors.forename: A Salam
authors.initials: AS
authors.lastname: Khan
authors.forename: Matthias
authors.initials: M
authors.lastname: Schad
authors.forename: Jörg
authors.initials: J
authors.lastname: Hacker
authors.forename: Rob M J
authors.initials: RM
authors.lastname: Liskamp
authors.forename: Roland J
authors.initials: RJ
authors.lastname: Pieters
mesh_terms: D001422:Bacterial Adhesion / Q000187:drug effects*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000138:chemical synthesis / Q000494:pharmacology*; D004187:Disaccharides / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000166:cytology / Q000187:drug effects* / Q000235:genetics; D010861:Fimbriae, Bacterial / Q000187:drug effects* / Q000378:metabolism; D020128:Inhibitory Concentration 50; D008024:Ligands; D008969:Molecular Sequence Data; D011550:Pseudomonas aeruginosa / Q000166:cytology / Q000187:drug effects* / Q000235:genetics
chemical_list: D002241:Carbohydrates; D004187:Disaccharides; D008024:Ligands