title: Inhibition of adhesion of type 1 fimbriated Escherichia coli to highly mannosylated ligands.
abstract: The inhibitory potencies of a number of mannosides, di- and trivalent mannosides, a set of mannose-terminating dendrimers, and five types of mannose-bearing neoglycoproteins were determined by using a binding assay that measures the binding of (125)I-labeled, highly mannosylated neoglycoprotein to a type 1 fimbriated Escherichia coli (K12) strain in suspension. The IC(50) values (the concentration of inhibitor that causes 50 % reduction in the bound (125)I-ligand to E. coli) obtained by this method were much lower than the equivalent values obtained by hemagglutination or in assays that involve microplate immobilization. Two important factors that strongly influence the affinity to E. coli adhesin are: 1) the presence of an alpha-oriented aglycon that has a long aliphatic chain or an aromatic group immediately next to the glycosyl oxygen, and 2) the presence of multiple mannosyl residues that can span a distance of 20 nm or longer on a relatively inflexible structure. The two best inhibitors, which are a highly mannosylated neoglycoprotein with the longest linking arm between a mannose and protein amino group and the largest mannosylated dendrimer (fourth generation), exhibited sub-nM IC(50) values.
authors.affiliation: Laboratory of Bioorganic Chemistry & Glycoclusters, Division of Biological Sciences, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Nagahori
authors.forename: Reiko T
authors.initials: RT
authors.lastname: Lee
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Nishimura
authors.forename: Daniel
authors.initials: D
authors.lastname: Pagé
authors.forename: René
authors.initials: R
authors.lastname: Roy
authors.forename: Yuan C
authors.initials: YC
authors.lastname: Lee
mesh_terms: D018830:Adhesins, Escherichia coli / Q000187:drug effects* / Q000378:metabolism; D001422:Bacterial Adhesion / Q000187:drug effects*; D004187:Disaccharides / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000166:cytology*; D010861:Fimbriae, Bacterial / Q000737:chemistry; D006023:Glycoproteins / Q000737:chemistry / Q000494:pharmacology; D006384:Hemagglutination / Q000187:drug effects; D020128:Inhibitory Concentration 50; D008024:Ligands; D046911:Macromolecular Substances; D008362:Mannosides / Q000737:chemistry / Q000494:pharmacology*; D011869:Radioligand Assay; D013329:Structure-Activity Relationship; D014312:Trisaccharides / Q000737:chemistry / Q000494:pharmacology
chemical_list: D018830:Adhesins, Escherichia coli; D004187:Disaccharides; D006023:Glycoproteins; D008024:Ligands; D046911:Macromolecular Substances; D008362:Mannosides; D014312:Trisaccharides