title: A novel synthetic Arg-Gly-Asp-containing peptide cyclo(-RGDf==V-) is the potent inhibitor of angiogenesis.
abstract: 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.
authors.affiliation: 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
authors.forename: M
authors.initials: M
authors.lastname: Kawaguchi
authors.forename: R
authors.initials: R
authors.lastname: Hosotani
authors.forename: S
authors.initials: S
authors.lastname: Ohishi
authors.forename: N
authors.initials: N
authors.lastname: Fujii
authors.forename: S S
authors.initials: SS
authors.lastname: Tulachan
authors.forename: M
authors.initials: M
authors.lastname: Koizumi
authors.forename: E
authors.initials: E
authors.lastname: Toyoda
authors.forename: T
authors.initials: T
authors.lastname: Masui
authors.forename: S
authors.initials: S
authors.lastname: Nakajima
authors.forename: S
authors.initials: S
authors.lastname: Tsuji
authors.forename: J
authors.initials: J
authors.lastname: Ida
authors.forename: K
authors.initials: K
authors.lastname: Fujimoto
authors.forename: M
authors.initials: M
authors.lastname: Wada
authors.forename: R
authors.initials: R
authors.lastname: Doi
authors.forename: M
authors.initials: M
authors.lastname: Imamura
mesh_terms: 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
chemical_list: D009842:Oligopeptides; D010456:Peptides, Cyclic; C047981:arginyl-glycyl-aspartic acid