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Rationally Designed Chemically Modified Glycodendrimer Inhibits Streptococcus suis Adhesin SadP at Picomolar Concentrations

Haataja, Sauli; Verma, Priya LU ; Fu, Ou; Papageorgiou, Anastassios C.; Pöysti, Sakari; Pieters, Roland J.; Nilsson, Ulf J. LU and Finne, Jukka (2018) In Chemistry - A European Journal 24(8). p.1905-1912
Abstract

Host cell surface carbohydrate receptors of bacterial adhesins are attractive targets in anti-adhesion therapy. The affinity of carbohydrate ligands with adhesins is usually found in the low μm range, which poses a problem for the design of effective inhibitors useful in therapy. In an attempt to increase the inhibitory power of carbohydrate ligands, we have combined the approach of chemical modification of ligands with their presentation as multivalent dendrimers in the design of an inhibitor of streptococcal adhesin SadP binding to its galactosyl-α1-4-galactose (galabiose) receptor. By using a phenylurea-modified galabiose-containing trisaccharide in a tetravalent dendrimeric scaffold, inhibition of adhesin at a low picomolar level... (More)

Host cell surface carbohydrate receptors of bacterial adhesins are attractive targets in anti-adhesion therapy. The affinity of carbohydrate ligands with adhesins is usually found in the low μm range, which poses a problem for the design of effective inhibitors useful in therapy. In an attempt to increase the inhibitory power of carbohydrate ligands, we have combined the approach of chemical modification of ligands with their presentation as multivalent dendrimers in the design of an inhibitor of streptococcal adhesin SadP binding to its galactosyl-α1-4-galactose (galabiose) receptor. By using a phenylurea-modified galabiose-containing trisaccharide in a tetravalent dendrimeric scaffold, inhibition of adhesin at a low picomolar level was achieved. This study has resulted in one of the most potent inhibitors observed for bacterial adhesins and demonstrates a promising approach to develop anti-adhesives with the potential of practical applicability.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
AlphaScreen, Bacterial adhesion, Carbohydrate receptors, Dendrimers, Glycolipids, Streptococcus suis
in
Chemistry - A European Journal
volume
24
issue
8
pages
1905 - 1912
publisher
John Wiley & Sons
external identifiers
  • scopus:85040028465
ISSN
0947-6539
DOI
10.1002/chem.201704493
language
English
LU publication?
yes
id
6b14bd42-fce6-43f2-baa8-7e55f291ce79
date added to LUP
2018-01-15 09:43:10
date last changed
2018-02-18 23:16:05
@article{6b14bd42-fce6-43f2-baa8-7e55f291ce79,
  abstract     = {<p>Host cell surface carbohydrate receptors of bacterial adhesins are attractive targets in anti-adhesion therapy. The affinity of carbohydrate ligands with adhesins is usually found in the low μm range, which poses a problem for the design of effective inhibitors useful in therapy. In an attempt to increase the inhibitory power of carbohydrate ligands, we have combined the approach of chemical modification of ligands with their presentation as multivalent dendrimers in the design of an inhibitor of streptococcal adhesin SadP binding to its galactosyl-α1-4-galactose (galabiose) receptor. By using a phenylurea-modified galabiose-containing trisaccharide in a tetravalent dendrimeric scaffold, inhibition of adhesin at a low picomolar level was achieved. This study has resulted in one of the most potent inhibitors observed for bacterial adhesins and demonstrates a promising approach to develop anti-adhesives with the potential of practical applicability.</p>},
  author       = {Haataja, Sauli and Verma, Priya and Fu, Ou and Papageorgiou, Anastassios C. and Pöysti, Sakari and Pieters, Roland J. and Nilsson, Ulf J. and Finne, Jukka},
  issn         = {0947-6539},
  keyword      = {AlphaScreen,Bacterial adhesion,Carbohydrate receptors,Dendrimers,Glycolipids,Streptococcus suis},
  language     = {eng},
  month        = {02},
  number       = {8},
  pages        = {1905--1912},
  publisher    = {John Wiley & Sons},
  series       = {Chemistry - A European Journal},
  title        = {Rationally Designed Chemically Modified Glycodendrimer Inhibits Streptococcus suis Adhesin SadP at Picomolar Concentrations},
  url          = {http://dx.doi.org/10.1002/chem.201704493},
  volume       = {24},
  year         = {2018},
}