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Journal of Biochemistry Advance Access originally published online on July 14, 2006
Journal of Biochemistry 2006 140(2):299-304; doi:10.1093/jb/mvj152
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© 2006 The Japanese Biochemical Society.

Regular Paper

NGR Enhanced the Anti-Angiogenic Activity of tum-5

Jieru Meng1,2,*, Nan Ma1,2,*, Zhen Yan1,2, Wei Han1,2,{dagger} and Yingqi Zhang1,2,{dagger}

1 Biotechnology Center of The Fourth Military Medical University, 17 Changle West Road, 710032 Xi'an, People's Republic of China; and 2 State Key Laboratory of Cancer Biology, 17 Changle West Road, 710032 Xi'an, People's Republic of China

{dagger} To whom correspondence should be addressed. Wei Han or Yingqi Zhang, Biotechnology Center, The Fourth Military Medical University, 17 Changle West Road, Xi'an, Shaanxi, 710032, P.R.China. Tel: +86-2984774775; Fax: +86-2983247213, E-mail: hanwwcn{at}yahoo.com.cn or zhangyqh{at}fmmu.edu.cn

Tumstatin is an angiogenesis inhibitor. The anti-angiogenic activity of tumstatin is localized to the 54–132 amino acids. NGR motif is a marker of angiogenic endothelial cells. We synthesized the gene fragment encoding the amino acids 45–132 of tumstatin (tum-5) and coupled a NGR (CNGRCVSGCAGRC) motif to the C-terminal of tum-5 (tum-5-NGR). The both were inserted into pQE30 expression vector and expressed in Escherichia coli. The anti-angiogenic effects of tum-5-NGR and tum-5 were examined in vivo. The results demonstrated the effect of the former was more significant than the latter. After S180 murine cancer xenografts in BALB/c mice were treated with tum-5-NGR or tum-5, tum-5-NGR displayed more significant tumor growth inhibition than tum-5. Binding of tum-5-NGR to normal and tumor tissues was also evaluated. The results showed that the accumulation of tum-5-NGR in tumor tissue was much more than in normal tissues. These data suggest that NGR enhance the anti-angiogenic activity of tum-5.

* These authors contributed equally to this article.


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