Solid-phase synthesis of cyclic RGD-furanoid sugar amino acid peptides as integrin inhibitors.
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.
van Well
Renate M
RM
Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands.
Overkleeft
Herman S
HS
van der Marel
Gijsbert A
GA
Bruss
Dan
D
Thibault
Gaétan
G
de Groot
Phillip G
PG
van Boom
Jacques H
JH
Overhand
Mark
M
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*
D007202:Indicators and Reagents; D039302:Integrin alphaVbeta3; D016023:Integrins; D009842:Oligopeptides; D040201:Platelet Membrane Glycoprotein IIb; D013400:Sugar Acids; C047981:arginyl-glycyl-aspartic acid