Design and synthesis of a new sialyl Lewis X mimetic: how selective are the selectin receptors?
The present paper reports the molecular modeling-based design and synthesis of an optically pure noncarbohydrate mimetic of sialyl Lewis X to inhibit E-selectin. Biological evaluation of the designed substance as well as that of its enantiomer gave, contrary to expectations, comparable IC50 values. Results are discussed in terms of receptor binding specificity and the molecular modeling protocol used.
De Vleeschauwer
M
M
Départment de chimie, Université de Montréal, Québec, Canada.
Vaillancourt
M
M
Goudreau
N
N
Guindon
Y
Y
Gravel
D
D
D002240:Carbohydrate Sequence; D019040:E-Selectin / Q000187:drug effects*; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry*; D016201:Receptors, Lymphocyte Homing / Q000187:drug effects*; D000080506:Sialyl Lewis X Antigen; D013237:Stereoisomerism
D019040:E-Selectin; D009844:Oligosaccharides; D016201:Receptors, Lymphocyte Homing; D000080506:Sialyl Lewis X Antigen