Beta-C-mannosides as selectin inhibitors.
Potential E- and P-selectin inhibitors were synthesized to explore a hydrophobic area on the E-selectin surface and the PSGL-1 protein binding site on the P-selectin surface that was recently defined by crystallography. Three series of mannose-based compounds (libraries A, B, and C) were synthesized using solution phase parallel synthesis. Biological evaluation of these compounds was done using two ELISA-based assays and transferred NOE (trNOE) experiments. Some of the compounds showed better activity than sLe(x) in the P-selectin assay.
Kaila
Neelu
N
Department of Chemical Sciences, Wyeth Research, 200 Cambridge Park Drive, Cambridge, Massachusetts 02140, USA. nkaila@war.wyeth.com
Chen
Lihren
L
Thomas
Bert E
BE
Tsao
Desiree
D
Tam
Steve
S
Bedard
Patricia W
PW
Camphausen
Raymond T
RT
Alvarez
Juan C
JC
Ullas
Giliyar
G
D020650:Combinatorial Chemistry Techniques; D018360:Crystallography, X-Ray; D019040:E-Selectin / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008362:Mannosides / Q000138:chemical synthesis* / Q000737:chemistry; D008562:Membrane Glycoproteins / Q000737:chemistry; D008958:Models, Molecular; D009844:Oligosaccharides / Q000737:chemistry; D019007:P-Selectin / Q000737:chemistry*; D011485:Protein Binding; D000080506:Sialyl Lewis X Antigen; D013329:Structure-Activity Relationship
D019040:E-Selectin; D008024:Ligands; D008362:Mannosides; D008562:Membrane Glycoproteins; D009844:Oligosaccharides; D019007:P-Selectin; C084882:P-selectin ligand protein; D000080506:Sialyl Lewis X Antigen