title: Beta-C-mannosides as selectin inhibitors.
abstract: 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.
authors.affiliation: Department of Chemical Sciences, Wyeth Research, 200 Cambridge Park Drive, Cambridge, Massachusetts 02140, USA. nkaila@war.wyeth.com
authors.forename: Neelu
authors.initials: N
authors.lastname: Kaila
authors.forename: Lihren
authors.initials: L
authors.lastname: Chen
authors.forename: Bert E
authors.initials: BE
authors.lastname: Thomas
authors.forename: Desiree
authors.initials: D
authors.lastname: Tsao
authors.forename: Steve
authors.initials: S
authors.lastname: Tam
authors.forename: Patricia W
authors.initials: PW
authors.lastname: Bedard
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Camphausen
authors.forename: Juan C
authors.initials: JC
authors.lastname: Alvarez
authors.forename: Giliyar
authors.initials: G
authors.lastname: Ullas
mesh_terms: 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
chemical_list: 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