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Cross-linking and sequence specific alkylation of DNA by aziridinyl quinones. 2. Structure requirements for sequence
R H Hargreaves1, S P Mayalarp, J Butler
1CRC Department of Biophysical Chemistry, Drug Development, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, U.K.
Abstract:
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 that the quinones which reacted randomly.