CROSS-LINKING AND SEQUENCE-SPECIFIC ALKYLATION OF DNA BY AZIRIDINYL QUINONES .2. STRUCTURE REQUIREMENTS FOR SEQUENCE SELECTIVITY

Authors
HARGREAVES RHJ MAYALARP SP BUTLER J MCADAM SR OHARE CC HARTLEY JA
Citation
Rhj. Hargreaves et al., CROSS-LINKING AND SEQUENCE-SPECIFIC ALKYLATION OF DNA BY AZIRIDINYL QUINONES .2. STRUCTURE REQUIREMENTS FOR SEQUENCE SELECTIVITY, Journal of medicinal chemistry, 40(3), 1997, pp. 357-361
Citations number
34
Categorie Soggetti
Chemistry Medicinal
Journal title
Journal of medicinal chemistry → ACNP
ISSN journal
00222623
Volume
40
Issue
3
Year of publication
1997
Pages
357 - 361
Database
ISI
SICI code
0022-2623(1997)40:3<357:CASAOD>2.0.ZU;2-Y
Abstract
The cytotoxicities and DNA sequence selectivity for guanine-N7 alkylat ion of 22 mono- and disubstituted 2,5-diaziridinyl-1,4-benzoquinones h ave been investigated. Several quinones produced patterns of alkylatio n 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 p ublished crystallographic data, was used to explain this selectivity. The sequence selective quinones were generally more cytotoxic than the quinones which reacted randomly.