1996 Fiscal Year Final Research Report Summary
Studies on Antitumor Cyclic Oligopeptides from Higher Plants
| Project/Area Number |
06403029
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | Tokyo University of Pharmacy & Life Science |
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Principal Investigator |
ITOKAWA Hideji Tokyo Uni.of Pharm.& Life Sci., Pharm., Prof., 薬学部, 教授 (60057304)
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| Co-Investigator(Kenkyū-buntansha) |
MORITA Hiroshi Tokyo Uni.of Pharm.& Life Sci., Pharm., Assistant, 薬学部, 助手 (70220069)
HITOTSUYANAGI Yukio Tokyo Uni.of Pharm.& Life Sci., Pharm., Lecturer, 薬学部, 講師 (80218726)
TAKEYA Koichi Tokyo Uni.of Pharm.& Life Sci., Pharm., Ass.Prof., 薬学部, 助教授 (20120149)
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| Project Period (FY) |
1994 – 1996
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| Keywords | antitumor activity / cyclic peptide / oligopeptide / conformation analysis / higher plant / structure-activity relationship / biological substance / structure elucidation |
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| Research Abstract |
Studies on Total Synthesis and Chemical Modification of Antitumor Cyclic Peptide RAs : Antitumor cyclic hexapeptide RAs are two ring system compounds, one moieties of which are 14-membered ring structures containing biphenyl ether bonds and their total syntheses are very difficult. But we have already demonstrated the total syntheses and the related various derivatives have been prepared. Then we found out some significant active compounds. In this time, further studies on the various side chain derivatives without basic moieties have been demonstrated and also promised potent compounds have been found out from the viewpoint of the suructure-activity relationship. Also the antitumor thiopeptides have been prepared from the cyclic hexapeptide RAs using Lawesson reagent. These antitumor cyclic thiopeptides showed generally more stronger activity than the original peptides. The clinical phase I studies of the antitumor cyclic hexapeptide RA-VII has been already performed and the clinical application is now in progress.
Identifies of Antitumor cyclic Peptides from Higher Plants without Rubia ones : Identifies of Antitumor cyclic Peptides from Higher Plants without Rubia ones have been also demonstrated. Then cyclic peptides have been isolated from Aster tataricus (Compositae), Pseudostellaria heterophylla (Caryophyllaceae) and Stellaria dichotoma (Caryophyllaceae) etc.and their further studies have been done. Also, the cyclic peptides have been obtained from Vaccaria segetalis and Lycium chinensis and their structures were elucidated by means of spectral and chemical analyzes. These bioactive cyclic peptides also have been studied from the viewpoints of conformational structures and bioactivities relationships using X-ray analysis, NMR techniques and Molecular Dynamics etc.
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