| 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
|
| Project Status |
Completed (Fiscal Year 2017)
|
| Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2016: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
|
|---|
| 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 / ヒト免疫不全ウイルス / 医薬品開発 / 中分子創薬 / 二次構造 / 2価型 / 二量体 / 高次構造模倣型 / 2価結合型GPCRリガンド |
|---|
| 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.
|
