title: Solid-phase synthesis of cyclic RGD-furanoid sugar amino acid peptides as integrin inhibitors.
abstract: The solid-phase synthesis of cyclic RGD peptides containing either one or two furanoid sugar amino acids (SAAs) is reported. Using a cyclization-cleavage approach five peptides were successfully assembled and consecutively tested on their ability to bind to the integrin receptors alpha(v)beta(3) and alpha(IIb)beta(3). The cyclic tetrapeptide c[RGD-SAA] (1) showed the most promising activity in an inhibition assay with an IC(50) of 1.49 microM for the alpha(v)beta(3) receptor and 384 nM for the alpha(IIb)beta(3) receptor.
authors.affiliation: Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands.
authors.forename: Renate M
authors.initials: RM
authors.lastname: van Well
authors.forename: Herman S
authors.initials: HS
authors.lastname: Overkleeft
authors.forename: Gijsbert A
authors.initials: GA
authors.lastname: van der Marel
authors.forename: Dan
authors.initials: D
authors.lastname: Bruss
authors.forename: Gaétan
authors.initials: G
authors.lastname: Thibault
authors.forename: Phillip G
authors.initials: PG
authors.lastname: de Groot
authors.forename: Jacques H
authors.initials: JH
authors.lastname: van Boom
authors.forename: Mark
authors.initials: M
authors.lastname: Overhand
mesh_terms: D001667:Binding, Competitive / Q000187:drug effects; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003500:Cyclization; D006801:Humans; D007202:Indicators and Reagents; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors / Q000097:blood; D016023:Integrins / Q000037:antagonists & inhibitors*; D009842:Oligopeptides / Q000138:chemical synthesis*; D010974:Platelet Aggregation / Q000187:drug effects; D040201:Platelet Membrane Glycoprotein IIb / Q000097:blood / Q000187:drug effects; D013400:Sugar Acids / Q000737:chemistry*
chemical_list: D007202:Indicators and Reagents; D039302:Integrin alphaVbeta3; D016023:Integrins; D009842:Oligopeptides; D040201:Platelet Membrane Glycoprotein IIb; D013400:Sugar Acids; C047981:arginyl-glycyl-aspartic acid