TY - JOUR
T1 - Quantitative studies of the binding of the class II PapG adhesin from uropathogenic Escherichia coli to oligosaccharides
AU - Larsson, Andreas
AU - Ohlsson, Jörgen
AU - Dodson, Karen W.
AU - Hultgren, Scott J.
AU - Nilsson, Ulf
AU - Kihlberg, Jan
N1 - Funding Information:
This work was funded by grants from the Swedish Research Council, the Göran Gustafsson Foundation for Research in Natural Sciences and Medicine, the Kempe Foundation, and the program ‘Glycoconjugates in Biological Systems’, sponsored by the Swedish Foundation for Strategic Research.
PY - 2003/5/15
Y1 - 2003/5/15
N2 - Binding of the class II PapG adhesin, found at the tip of filamentous pili on Escherichia coli, to the carbohydrate moiety of globoseries glycolipids in the human kidney is a key step in development of pyelonephritis, a severe form of urinary tract infection. An assay based on surface plasmon resonance for quantification of the binding of the class II PapG adhesin to oligosaccharides has been developed. Using this assay dissociation constants ranging from 80 to 540 μM were determined for binding of the PapG adhesin to di-pentasaccharide fragments from the globoseries of glycolipids. A series of galabiose derivatives, modified at the anomeric position, O-2′ or O-3′, was also investigated. The anomeric position appeared to be the most promising for development of improved inhibitors of PapG-mediated adhesion of E. coli. p-Methoxyphenyl galabioside was found to be most potent (Kd=140 μM), and binds to PapG almost as well as the Forssman pentasaccharide.
AB - Binding of the class II PapG adhesin, found at the tip of filamentous pili on Escherichia coli, to the carbohydrate moiety of globoseries glycolipids in the human kidney is a key step in development of pyelonephritis, a severe form of urinary tract infection. An assay based on surface plasmon resonance for quantification of the binding of the class II PapG adhesin to oligosaccharides has been developed. Using this assay dissociation constants ranging from 80 to 540 μM were determined for binding of the PapG adhesin to di-pentasaccharide fragments from the globoseries of glycolipids. A series of galabiose derivatives, modified at the anomeric position, O-2′ or O-3′, was also investigated. The anomeric position appeared to be the most promising for development of improved inhibitors of PapG-mediated adhesion of E. coli. p-Methoxyphenyl galabioside was found to be most potent (Kd=140 μM), and binds to PapG almost as well as the Forssman pentasaccharide.
UR - http://www.scopus.com/inward/record.url?scp=0344490325&partnerID=8YFLogxK
U2 - 10.1016/S0968-0896(03)00114-7
DO - 10.1016/S0968-0896(03)00114-7
M3 - Article
C2 - 12713835
AN - SCOPUS:0344490325
SN - 0968-0896
VL - 11
SP - 2255
EP - 2261
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 10
ER -