Nonpeptide RGD antagonists: a novel class of mimetics, the 5,8-disubstituted 1-azabicyclo[5.2.0]nonan-2-one lactam.
The 1-azabicyclo[5.2.0]nonan-2-one lactam 1 adequately substituted on both cycles A and B as scaffolds mimics the conformationally constrained beta-turn of the tripeptide RGD signaling motif of fibronectin. Using an in vitro assay, we establish that trans diastereoisomer 1b dissociates a soluble fibronectin-integrin alpha(5)beta(1) complex at concentrations comparable to those of a linear RGDS peptide as a competitor.
Bourguet
Erika
E
Laboratoire de Chimie Biomoléculaire et Interactions Biologiques, Unité Mixte de Recherche CNRS 5074, Université Montpellier I, Faculté de Pharmacie, 15 Av. C. Flahault, BP 14491, 34093 Montpellier Cedex 5, France.
Banères
Jean-Louis
JL
Parello
Joseph
J
Lusinchi
Xavier
X
Girard
Jean-Pierre
JP
Vidal
Jean-Pierre
JP
D020816:Amino Acid Motifs; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D005353:Fibronectins / Q000737:chemistry; D039081:Integrin alpha5beta1 / Q000737:chemistry; D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013237:Stereoisomerism
C479983:1-azabicyclo(5.2.0)nonan-2-one lactam; D001643:Bridged Bicyclo Compounds; D005353:Fibronectins; D039081:Integrin alpha5beta1; D007769:Lactams; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid