A novel synthetic Arg-Gly-Asp-containing peptide cyclo(-RGDf==V-) is the potent inhibitor of angiogenesis.
Arg-Gly-Asp (RGD)-containing peptide is a ligand for integrin alpha(V)beta3 and acts as an angiogenic inhibitor. A novel cyclic RGD peptide, cyclo(-RGDf==V-) (f==V), was synthesized and its biological activities were characterized and compared with its analogs, cyclo(-RGDfV-) (fV) and cyclo(-RGDf-MeV-) (fMeV). It bound to integrin alpha(V)beta3 with almost the same affinity as the fV and fMeV analogs. All three compounds inhibited the adhesion and growth of HUVEC cells in a dose-dependent manner in vitro. Out of three, fMeV had the strongest effect, f==V was almost as strong as fMeV, and fV had the least effect. However, in vivo, f==V significantly decreased the intratumoral microvessel density (MVD) in the DLD-1 (human colon cancer cell) inoculated mice, while fMeV had little effect. These results suggest the potential usefulness of the cyclo(-RGDf==V-) as an antiangiogenic agent for clinical use in the future.
Kawaguchi
M
M
Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan. Michiya.Kawaguchi@ma3.seikyou.ne.jp
Hosotani
R
R
Ohishi
S
S
Fujii
N
N
Tulachan
S S
SS
Koizumi
M
M
Toyoda
E
E
Masui
T
T
Nakajima
S
S
Tsuji
S
S
Ida
J
J
Fujimoto
K
K
Wada
M
M
Doi
R
R
Imamura
M
M
D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology*; D009842:Oligopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000494:pharmacology* / Q000627:therapeutic use
D009842:Oligopeptides; D010456:Peptides, Cyclic; C047981:arginyl-glycyl-aspartic acid