TY - JOUR
T1 - A novel synthetic Arg-Gly-Asp-containing peptide cyclo(-RGDf=V-) is the potent inhibitor of angiogenesis
AU - Kawaguchi, Michiya
AU - Hosotani, Ryo
AU - Ohishi, Shinya
AU - Fujii, Nobutaka
AU - Singh Tulachan, Sidhartha
AU - Koizumi, Masayuki
AU - Toyoda, Eiji
AU - Masui, Toshihiko
AU - Nakajima, Sanae
AU - Tsuji, Shouichiro
AU - Ida, Jun
AU - Fujimoto, Koji
AU - Wada, Michihiko
AU - Doi, Ryuichiro
AU - Imamura, Masayuki
N1 - Funding Information:
This work was supported in part by a Grant-in-Aid for Scientific Research from the Japan Ministry of Education, Science and Culture. We thank Y. Tani (DAKO), N. Yawata, and K. Ajito (Meiji Pharmaceuticals) for their excellent technical support.
PY - 2001/11/2
Y1 - 2001/11/2
N2 - Arg-Gly-Asp (RGD)-containing peptide is a ligand for integrin αvβ3 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 αvβ3 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.
AB - Arg-Gly-Asp (RGD)-containing peptide is a ligand for integrin αvβ3 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 αvβ3 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.
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U2 - 10.1006/bbrc.2001.5809
DO - 10.1006/bbrc.2001.5809
M3 - Article
C2 - 11676501
AN - SCOPUS:0035798080
SN - 0006-291X
VL - 288
SP - 711
EP - 717
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -