A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Rationally Designed Chemically Modified Glycodendrimer Inhibits Streptococcus suis Adhesin SadP at Picomolar Concentrations.
Tekijät: Sauli Haataja, Priya Verma, Ou Fu, Anastassios C. Papageorgiou, Sakari Pöysti, Roland J. Pieters, Ulf J. Nilsson, Jukka Finne
Julkaisuvuosi: 2018
Journal: Chemistry - A European Journal
Tietokannassa oleva lehden nimi: Chemistry (Weinheim an der Bergstrasse, Germany)
Lehden akronyymi: Chemistry
Vuosikerta: 24
Numero: 8
Aloitussivu: 1905
Lopetussivu: 1912
Sivujen määrä: 8
ISSN: 1521-3765
DOI: https://doi.org/10.1002/chem.201704493
Tiivistelmä
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.
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