Development of mid-size drugs based on peptidomimetic

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04652
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: TAMAMURA Hirokazu 東京医科歯科大学, 生体材料工学研究所, 教授 (80217182)
• Co-Investigator(Kenkyū-buntansha): 野村 渉 東京医科歯科大学, 生体材料工学研究所, 准教授 (80463909) ; 水口 貴章 東京医科歯科大学, 生体材料工学研究所, 助教 (30732557) ; 大橋 南美 東京医科歯科大学, 生体材料工学研究所, 助教 (90707051)
• Research Collaborator: YOSHIMURA Kazuhisa ; MURAKAMI Tsutomu
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 中分子 / ペプチドミメティック / 環状ペプチド / HIV / がん / ステープルペプチド / CXCR4 / GPCR

Outline of Final Research Achievements

Peptidomimetics that mimic conformation such as secondary and tertiary structures of peptides/proteins have led to the recent development of anti-cancer and anti-HIV agents. Some examples are described as follows. Chemokine receptor CXCR4 antagonists based on cyclic peptides having conformationally constrained structures have been synthesized as agents with anti-chemotactic activity against cancer cells and inhibitory activity against HIV entry. HIV protein-derived stapled peptides with helix mimetics have been developed as HIV integrase inhibitors. Dimer and trimer mimetics of a C-terminal helical region (CHR/C34) of an envelope protein gp41 have been developed as HIV fusion inhibitors. In addition, bivalent ligands based on the above CXCR4 antagonists such as 14-mer peptide T140 derivatives have been synthesized to produce effective metastatic inhibition with the therapeutic potential. Taken together, these advantaged of mid-size drugs were shown.

Free Research Field

創薬化学