Rationally Designed Chemically Modified Glycodendrimer Inhibits Streptococcus suis Adhesin SadP at Picomolar Concentrations
(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
- Haataja, Sauli ; Verma, Priya LU ; Fu, Ou ; Papageorgiou, Anastassios C. ; Pöysti, Sakari ; Pieters, Roland J. ; Nilsson, Ulf J. LU and Finne, Jukka
- organization
- publishing date
- 2018-02-06
- 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
- Wiley-Blackwell
- external identifiers
-
- pmid:29094420
- 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
- 2024-07-08 07:37:42
@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}}, keywords = {{AlphaScreen; Bacterial adhesion; Carbohydrate receptors; Dendrimers; Glycolipids; Streptococcus suis}}, language = {{eng}}, month = {{02}}, number = {{8}}, pages = {{1905--1912}}, publisher = {{Wiley-Blackwell}}, 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}}, doi = {{10.1002/chem.201704493}}, volume = {{24}}, year = {{2018}}, }