A1 Refereed original research article in a scientific journal
Rationally Designed Chemically Modified Glycodendrimer Inhibits Streptococcus suis Adhesin SadP at Picomolar Concentrations.
Authors: Sauli Haataja, Priya Verma, Ou Fu, Anastassios C. Papageorgiou, Sakari Pöysti, Roland J. Pieters, Ulf J. Nilsson, Jukka Finne
Publication year: 2018
Journal: Chemistry - A European Journal
Journal name in source: Chemistry (Weinheim an der Bergstrasse, Germany)
Journal acronym: Chemistry
Volume: 24
Issue: 8
First page : 1905
Last page: 1912
Number of pages: 8
ISSN: 1521-3765
DOI: https://doi.org/10.1002/chem.201704493
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 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.
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.
UTU Research Portal