Synthesis of fluorinated C-mannopeptides as sialyl Lewisx mimics for E- and P-selectin inhibition.
The synthesis of fluorinated C-mannopeptides and their evaluation as E- and P-selectin inhibitors is described. These molecules are difluorinated analogues of CH(2)-glycopeptides already reported to act as sLe(x) mimics. The alpha and beta anomers of these CF(2)-glycopeptides have been prepared, as well as their 1-hydroxy analogues which were present in solution as an equilibrium mixture of alpha- and beta-pyranose and alpha- and beta-furanose forms. These molecules showed inhibitory activities comparable to their CH(2) counterparts with a moderate influence of the pseudo-anomeric center configuration.
Gouge-Ibert
Vanessa
V
Université et INSA de Rouen, CNRS, UMR6014 & FR3038-IRCOF, Mont Saint-Aignan Cedex, France.
Pierry
Camille
C
Poulain
Florent
F
Serre
Anne-Lise
AL
Largeau
Céline
C
Escriou
Virginie
V
Scherman
Daniel
D
Jubault
Philippe
P
Quirion
Jean-Charles
JC
Leclerc
Eric
E
D019040:E-Selectin / Q000187:drug effects*; D005461:Fluorine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D018716:Molecular Mimicry; D009844:Oligosaccharides / Q000737:chemistry*; D019007:P-Selectin / Q000037:antagonists & inhibitors*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000080506:Sialyl Lewis X Antigen
D019040:E-Selectin; D009844:Oligosaccharides; D019007:P-Selectin; D010455:Peptides; D000080506:Sialyl Lewis X Antigen; D005461:Fluorine