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

Ohlsson, Jörgen LU ; Larsson, A; Haataja, S; Alajääski, J; Stenlund, P; Pinkner, J; Hultgren, S; Finne, J; Kihlberg, J and Nilsson, Ulf LU (2005) In Organic and Biomolecular Chemistry 3(5). p.886-900
Abstract
Four collections of Gal1-4Gal 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 C1, 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... (More)
Four collections of Gal1-4Gal 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 C1, 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Organic and Biomolecular Chemistry
volume
3
issue
5
pages
886 - 900
publisher
Royal Society of Chemistry
external identifiers
  • wos:000227218500025
  • pmid:15731876
  • scopus:20144369748
ISSN
1477-0539
DOI
10.1039/b416878j
language
English
LU publication?
yes
id
929a9971-9602-4d56-b845-75d079103e26 (old id 158699)
date added to LUP
2007-07-10 13:23:35
date last changed
2017-04-02 03:25:47
@article{929a9971-9602-4d56-b845-75d079103e26,
  abstract     = {Four collections of Gal1-4Gal 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 C1, 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.},
  author       = {Ohlsson, Jörgen and Larsson, A and Haataja, S and Alajääski, J and Stenlund, P and Pinkner, J and Hultgren, S and Finne, J and Kihlberg, J and Nilsson, Ulf},
  issn         = {1477-0539},
  language     = {eng},
  number       = {5},
  pages        = {886--900},
  publisher    = {Royal Society of Chemistry},
  series       = {Organic and Biomolecular Chemistry},
  title        = {Structure–activity relationships of galabioside derivatives as inhibitors of E. coli and S. suis adhesins: nanomolar inhibitors of S. suis adhesins},
  url          = {http://dx.doi.org/10.1039/b416878j},
  volume       = {3},
  year         = {2005},
}