Structure-activity relationships of galabioside derivatives as inhibitors of E. coli and S. suis adhesins: Nanomolar inhibitors of S. suis adhesins

Jörgen Ohlsson, Andreas Larsson, Sauli Haataja, Jenny Alajääski, Peter Stenlund, Jerome S. Pinkner, Scott J. Hultgren, Finne Jukka, Jan Kihlberg, Ulf J. Nilsson

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Four collections of Galα1-4Gal derivatives were synthesised and evaluated as inhibitors of the PapG class II adhesin of uropathogenic Escherichia coli and of the PN and PO adhesins of Streptococcus suis strains. Galabiosides carrying aromatic structures at Cl, methoxyphenyl O-galabiosides in particular, were identified as potent inhibitors of the PapG adhesin. Phenylurea derivatisation at C3′ and methoxymethylation at O2′ of galabiose provided inhibitors of the S. suis strains type PN adhesin with remarkably high affinities (30 and 50 nM, respectively). In addition, quantitative structure-activity relationship models for E. coli PapG adhesin and S. suis adhesin type PO were developed using multivariate data analysis. The inhibitory lead structures constitute an advancement towards high-affinity inhibitors as potential anti-adhesion therapeutic agents targeting bacterial infections.

Original languageEnglish
Pages (from-to)886-900
Number of pages15
JournalOrganic and Biomolecular Chemistry
Volume3
Issue number5
DOIs
StatePublished - Mar 7 2005

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