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Discovery of Potent Inhibitors of PapG Adhesins from Uropathogenic Escherichia coli through Synthesis and Evaluation of Galabiose Derivatives
Author(s) -
Ohlsson Jörgen,
Jass Jana,
Uhlin Bernt Eric,
Kihlberg Jan,
Nilsson Ulf J.
Publication year - 2002
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/1439-7633(20020802)3:8<772::aid-cbic772>3.0.co;2-8
Subject(s) - bacterial adhesin , escherichia coli , stereochemistry , disaccharide , chemistry , biochemistry , microbiology and biotechnology , biology , gene
The synthesis of two galabioside (Gal α 1‐4Gal) collections based on diversification at the O‐1 and O‐3′ atoms is reported. The galabiosides were evaluated as inhibitors of hemagglutination of human erythrocytes by two strains of Escherichia coli that expressed the class I and class II PapG adhesins, respectively. The class I adhesin was found to prefer aromatic substituents both at the O‐1 and the O‐3′ position of the galabiose disaccharide. One galabioside , p ‐methoxyphenyl [3‐ O ‐( m ‐nitrobenzyl)‐ α ‐ D ‐galactopyranosyl]‐(1‐4)‐ β ‐ D ‐galactopyranoside], had an IC 50 value of 4.1 μ M , which is the best inhibition of the class I adhesin to date. In the case of the class II adhesin, one inhibitor, 2‐[( S )‐2‐methoxycarbonyl‐2‐acetamido‐ethylthio]ethyl {3‐ O ‐3‐[2‐(methoxycarbonylphenylthio)propyl]‐ α ‐ D ‐galactopyranosyl}‐(1‐4)‐ α ‐ D ‐galactopyranoside, was found to have an IC 50 value of 68 μ M , which is the best artificial inhibition of the class II adhesin reported so far with an affinity for the adhesin comparable to that of the natural tetrasaccharide ligand globotetraose.