The conformational behaviour and P-selectin inhibition of fluorine-containing sialyl LeX glycomimetics.
A combination of experimental J/NOE NMR data with molecular mechanics and dynamics calculations has been used to examine the conformational behaviour and assign the configuration of synthetically prepared epimeric 3-carboxymethyl-O-Gal-(1-->1)-alpha-Man-fluoro-C-glycosides. It is shown that the population distributions around the glycosidic linkages strongly depend on the configuration at the fluorinated carbon of the pseudoacetal residue. It is also shown that these compounds resemble the inhibition ability of sialyl LeX towards P-selectin.
Pérez-Castells
Javier
J
Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain. jjbarbero@cib.csic.es. jpercas@ceu.es
Hernández-Gay
José Juan
JJ
Denton
Richard W
RW
Tony
Kurissery A
KA
Mootoo
David R
DR
Jiménez-Barbero
Jesús
J
D002236:Carbohydrate Conformation; D003198:Computer Simulation; D006027:Glycosides / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods / Q000592:standards; D008956:Models, Chemical; D008958:Models, Molecular; D018716:Molecular Mimicry; D009844:Oligosaccharides / Q000737:chemistry*; D019007:P-Selectin / Q000737:chemistry*; D012015:Reference Standards; D012680:Sensitivity and Specificity; D000080506:Sialyl Lewis X Antigen; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013997:Time Factors
D006027:Glycosides; D009844:Oligosaccharides; D019007:P-Selectin; D000080506:Sialyl Lewis X Antigen