title: Interaction between the pili of Pseudomonas aeruginosa PAK and its carbohydrate receptor beta-D-GalNAc(1-->4)beta-D-Gal analogs.
abstract: Pseudomonas aeruginosa employs pili to mediate adherence to epithelial cell surface receptors. Previously, it has been shown that the pilus adhesin of P. aeruginosa PAK binds to the ganglioside asialo-GM1. In particular, it was found that the carbohydrate sequence beta-D-GalNAc(1-->4)beta-D-Gal is the minimal carbohydrate receptor sequence of asialo-GM1. To study the binding specificity of P. aeruginosa, O-modified and N-modified sugar analogs, where each hydroxyl group was substituted either by O-methyl or O-propyl and the acetamido group was changed to a propionamido group, were synthesized. The sugar analogs were evaluated as inhibitors in a competitive solid phase binding assay. The results demonstrate that the pili of P. aeruginosa PAK accepts a variety of sugar analogs possessing the sequence beta-D-GalNAc(1-->4)beta-D-Gal. Most sugar analogs bind with a similar order of magnitude (50% inhibitory concentration (IC50) = 60-130 microM) except for the 2-O-propyl derivative 7 (IC50 = 8 +/- 4 microM) compared with an IC50 of 79 +/- 18 microM for the native compound. The significant increase in binding affinity of 2-O-propyl derivative 7 suggests that improved inhibitors of adhesion may be prepared by introducing a hydrophobic side chain at the 2-position of galactose.
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Schweizer
authors.forename: H
authors.initials: H
authors.lastname: Jiao
authors.forename: O
authors.initials: O
authors.lastname: Hindsgaul
authors.forename: W Y
authors.initials: WY
authors.lastname: Wong
authors.forename: R T
authors.initials: RT
authors.lastname: Irvin
mesh_terms: D001422:Bacterial Adhesion; D001665:Binding Sites; D001667:Binding, Competitive; D050260:Carbohydrate Metabolism; D002240:Carbohydrate Sequence; D004848:Epithelium / Q000378:metabolism; D010861:Fimbriae, Bacterial / Q000378:metabolism*; D005677:G(M1) Ganglioside / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*
chemical_list: D011971:Receptors, Immunologic; C037872:pili, bacterial receptor; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside