Cross-linking and sequence specific alkylation of DNA by aziridinyl quinones .2. Structure requirements for sequence selectivity

被引：19

作者：

Hargreaves, RHJ

Mayalarp, SP

Butler, J

McAdam, SR

OHare, CC

Hartley, JA

机构：

[1] CHRISTIE HOSP NHS TRUST,PATERSON INST CANC RES,DEPT BIOPHYS CHEM,CRC,MANCHESTER M20 9BX,LANCS,ENGLAND

[2] UNIV COLL & MIDDLESEX SCH MED,DEPT ONCOL,DNA INTERACT RES GRP,CRC DRUG,LONDON W1P 8BT,ENGLAND

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1997年 / 40卷 / 03期

关键词：

D O I：

10.1021/jm960492j

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The cytotoxicities and DNA sequence selectivity for guanine-N7 alkylation of 22 mono- and disubstituted 2,5-diaziridinyl-1,4-benzoquinones have been investigated. Several quinones produced patterns of alkylation following reduction with a selectivity for 5'-TGC-3' sequences. This sequence selectivity appeared to be dependent only on the presence of a hydrogen in position-6 of the quinone. A computer model, based on published crystallographic data, was used to explain this selectivity. The sequence selective quinones were generally more cytotoxic than the quinones which reacted randomly.

引用

页码：357 / 361

页数：5

共 34 条

[1] DNA-DNA INTERSTRAND CROSS-LINKING BY 2,5-BIS(1-AZIRIDINYL)-3,6-BIS(CARBETHOXYAMINO)-1,4-BENZOQUINONE - COVALENT STRUCTURE OF THE DG-TO-DG CROSS-LINKS IN CALF THYMUS DNA AND A SYNTHETIC DNA DUPLEX [J].