tailieunhanh - Báo cáo hóa học: " Designed hybrid TPR peptide targeting Hsp90 as a novel anticancer agent"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: Designed hybrid TPR peptide targeting Hsp90 as a novel anticancer agent | Horibe et al. Journal of Translational Medicine 2011 9 8 http content 9 1 8 TRANSLATIONAL MEDICINE RESEARCH Open Access Designed hybrid TPR peptide targeting Hsp90 as a novel anticancer agent Tomohisa Horibe Masayuki Kohno Mari Haramoto Koji Ohara Koji Kawakami Abstract 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. Background Heat-shock protein 90 Hsp90 is a molecular chaperone 1 that participates in the quality control of protein folding. The mechanism of action of Hsp90 includes sequential ATPase cycles and the stepwise recruitment of cochaperones including Hsp70 CDC37 p60 Hsp-orga-nizing protein Hop and p23 2 3 . In particular Hsp90 and Hsp70 interact