A potent integrin antagonist from a small library of cyclic RGD pentapeptide mimics including benzyl-substituted azabicycloalkane amino acids.
A small library of cyclic RGD pentapeptide mimics, including benzyl-substituted azabicycloalkane amino acids, was synthesized with the aim of developing active and selective integrin antagonists. In vitro binding assays established one particular compound with affinity for both the alpha(v)beta(3) and the alpha(v)beta(5) integrins. The synthesis in solution and the in vitro screening of these RGD derivatives, as well as the determination of the conformational properties of the integrin ligands by spectroscopic and computational methods are described.
Arosio
Daniela
D
Istituto di Scienze e Tecnologie Molecolari, Consiglio Nazionale delle Ricerche, Via Fantoli 16/15, 20138 Milano, Italy.
Belvisi
Laura
L
Colombo
Lino
L
Colombo
Matteo
M
Invernizzi
Donatella
D
Manzoni
Leonardo
L
Potenza
Donatella
D
Serra
Massimo
M
Castorina
Massimo
M
Pisano
Claudio
C
Scolastico
Carlo
C
D053961:Azabicyclo Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000378:metabolism; D054852:Small Molecule Libraries
D053961:Azabicyclo Compounds; D016023:Integrins; D010456:Peptides, Cyclic; D054852:Small Molecule Libraries; C507169:cyclic arginine-glycine-aspartic acid peptide