Solid-phase synthesis of cyclic RGD-furanoid sugar amino acid peptides as integrin inhibitors

Renate M van Well; Herman S Overkleeft; Gijsbert A van der Marel; Dan Bruss; Gaétan Thibault; Phillip G de Groot; Jacques H van Boom; Mark Overhand

doi:10.1016/s0960-894x(02)01022-3

Solid-phase synthesis of cyclic RGD-furanoid sugar amino acid peptides as integrin inhibitors

Bioorg Med Chem Lett. 2003 Feb 10;13(3):331-4. doi: 10.1016/s0960-894x(02)01022-3.

Authors

Renate M van Well¹, Herman S Overkleeft, Gijsbert A van der Marel, Dan Bruss, Gaétan Thibault, Phillip G de Groot, Jacques H van Boom, Mark Overhand

Affiliation

¹ Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands.

PMID: 12565923
DOI: 10.1016/s0960-894x(02)01022-3

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.

MeSH terms

Binding, Competitive / drug effects
Blood Coagulation / drug effects
Blood Platelets / chemistry
Chromatography, High Pressure Liquid
Cyclization
Humans
Indicators and Reagents
Integrin alphaVbeta3 / antagonists & inhibitors
Integrin alphaVbeta3 / blood
Integrins / antagonists & inhibitors*
Oligopeptides / chemical synthesis*
Platelet Aggregation / drug effects
Platelet Membrane Glycoprotein IIb / blood
Platelet Membrane Glycoprotein IIb / drug effects
Sugar Acids / chemistry*

Substances

Indicators and Reagents
Integrin alphaVbeta3
Integrins
Oligopeptides
Platelet Membrane Glycoprotein IIb
Sugar Acids
arginyl-glycyl-aspartic acid