VINYL EPOXIDES - REAGENTS FOR RADICAL-INDUCED DNA CLEAVAGE

被引：12

作者：

BREEN, AP ^{[1
]}

MURPHY, JA ^{[1
]}

机构：

[1] UNIV NOTTINGHAM,DEPT CHEM,UNIV PK,NOTTINGHAM NG7 2RD,ENGLAND

来源：

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1 | 1993年 / 23期

关键词：

D O I：

10.1039/p19930002979

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Allyloxyl radicals,formed by addition of thiyl radicals to vinyl epoxides, function as DNA-cleaving agents. Radical-induced damage to DNA is normally caused either by hydrogen-atom abstraction from deoxyribose or addition to the pi-bonds of the heterocyclic bases. Model studies showed that allyloxyl radicals could effect both hydrogen-atom abstraction and addition to simple alkene pi-bonds (but no product of addition to the pi-bonds of adenine was observed). Importantly, this model chemistry could be performed in water at room temperature, and using enzymic formation of glutathionyl radicals. An intercalating vinyl epoxide 35 bound to PHIX174 supercoiled DNA caused cleavage when activated by glutathionyl radicals. The potential use of epoxide 35 in reversing the radiation resistance of tumours with a high local concentration of glutathione is discussed.

引用

页码：2979 / 2990

页数：12

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