Photocross-11nklng and the Cleavage of DNA by Iron Complex-Substituted Psoralen

1998 Fiscal Year Final Research Report Summary

• Project/Area Number: 09672289
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 医薬分子機能学
• Research Institution: SCIENCE UNIVERSITY OF TOKYO
• Principal Investigator: NAKAMURA Yushin SCIENCE UNIVERSITY OF TOKYO,Biologycal Science and Technology, Professor, 基礎工学部, 教授 (60118536)
• Co-Investigator(Kenkyū-buntansha): HASHIMOTO Shigeki , 助手 (10287477)
• Project Period (FY): 1997 – 1998
• Keywords: PSORALEN / PHOTOCROSS-LINKING / DNA CLEAVAGE / BLEOMYCIN MODEL / KB CELL / APOPTOSIS

Research Abstract

The failure of bleomycin to cause mutagenesis may be a result of the killing of cells due to irreparable damage of DNA caused by highly double strand breaks. We designed a new type of DNA cleavage agent, iron complex-substituted psoralen (1) according to the following strategy and is essentially composed of following three parts : (A ) a moiety capable of photochemically cross-linking to DNA ; (B) a DNA cleaving moiety ; (C) a linker moiety connecting (A) and (B) having a high binding affinity to DNA.A psuralen was used as (A) , an iron-complexing group as cleaving moiety (B) which has been synthesized as a bleomycin model, and polymethylene-amides as a llnker (C). The photoreaction of which is noniron complex of 1, with Col El plasmld DNA gave the covalently interstrand cross - linked DNA which was caused the high double strand scissions in the presence of FeSO4 and dithiothreitol under air. The inhibision effect and apoptosis to KB cells of 1 were observed.