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Designed hybrid TPR peptide targeting Hsp90 as a novel anticancer agent

Designed hybrid TPR peptide targeting Hsp90 as a novel anticancer agent,10.1186/1479-5876-9-8,Journal of Translational Medicine,Tomohisa Horibe,Masayu

Designed hybrid TPR peptide targeting Hsp90 as a novel anticancer agent   (Citations: 2)
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BACKGROUND: Despite an ever-improving understanding of the molecular biology of cancer, the treatment of most cancers has not changed dramatically in the past three decades and drugs that do not discriminate between tumor cells and normal tissues remain the mainstays of anticancer therapy. Since Hsp90 is typically involved in cell proliferation and survival, this is thought to play a key role in cancer, and Hsp90 has attracted considerable interest in recent years as a potential therapeutic target. METHODS: We focused on the interaction of Hsp90 with its cofactor protein p60/Hop, and engineered a cell-permeable peptidomimetic, termed "hybrid Antp-TPR peptide", modeled on the binding interface between the molecular chaperone Hsp90 and the TPR2A domain of Hop. RESULTS: It was demonstrated that this designed hybrid Antp-TPR peptide inhibited the interaction of Hsp90 with the TPR2A domain, inducing cell death of breast, pancreatic, renal, lung, prostate, and gastric cancer cell lines in vitro. In contrast, Antp-TPR peptide did not affect the viability of normal cells. Moreover, analysis in vivo revealed that Antp-TPR peptide displayed a significant antitumor activity in a xenograft model of human pancreatic cancer in mice. CONCLUSION: These results indicate that Antp-TPR peptide would provide a potent and selective anticancer therapy to cancer patients.
Journal: Journal of Translational Medicine - J TRANSL MED , vol. 9, no. 1, pp. 8-12, 2011
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