Optimization of RGD-containing cyclic peptides against αvβ3 integrin

Yan Wang, Wenwu Xiao, Yonghong Zhang, Leah Meza, Harry Tseng, Yoshikazu Takada, James B. Ames, Kit S. Lam

研究成果: 雜誌貢獻文章同行評審

39 引文 斯高帕斯(Scopus)


We have previously reported the use of one-bead-one-compound (OBOC) combinatorial technology to develop a disulfide cyclic, Arg-Gly-Asp-containing octapeptide LXW7 (cGRGDdvc), that targets αvβ3 integrin with high affinity and specificity. αvβ3 integrin is known to be overexpressed in many cancers and in tumor vasculature, and it has been established as a cancer therapeutic target. To further optimize LXW7, we have performed systematic structure-activity relationship studies. On the basis of the results, two highly focused OBOC peptide libraries were designed, synthesized, and screened against αvβ3 integrin-transfected K562 cells. One of the best ligands, LXW64, was found to have 6.6-fold higher binding affinity than LXW7, and showed preferential binding to cells expressing αvβ3 integrin. In addition to binding strongly to U-87MG glioblastoma cells in vitro, LXW64 also targets U-87MG xenografts implanted in nude mice, indicating that it is an excellent vehicle for the delivery of cytotoxic payload to tumors and tumor blood vessels that overexpress αvβ3 integrin.

頁(從 - 到)232-240
期刊Molecular Cancer Therapeutics
出版狀態已發佈 - 2月 2016

ASJC Scopus subject areas

  • 腫瘤科
  • 癌症研究


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