Molecular dynamics reveal that isoDGR-containing cyclopeptides are true αvβ3 antagonists unable to promote integrin allostery and activation.
Ain't got that swing(-out): The cyclopeptide isoDGR is emerging as a new αvβ3 integrin binding motif. Agreement between the results of computational and biochemical studies reveals that isoDGR-containing cyclopeptides are true αvβ3 integrin antagonists that block αvβ3 in its inactive conformation (see scheme). isoDGR-based ligands may give αvβ3 antagonists without paradoxical effects.
Dulbecco Telethon Institute, Biomolecular NMR Laboratory c/o Ospedale S. Raffaele via Olgettina 58, 20132 Milan, Italy.
Michela
M
Ghitti
Andrea
A
Spitaleri
Barbara
B
Valentinis
Silvia
S
Mari
Claudia
C
Asperti
Catia
C
Traversari
Gian Paolo
GP
Rizzardi
Giovanna
G
Musco
D000494:Allosteric Regulation; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*
D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D010456:Peptides, Cyclic; C047981:arginyl-glycyl-aspartic acid