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

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

  • J Med Chem. 1997 Jan 31;40(3):357-61. doi: 10.1021/jm960492j.
R H Hargreaves 1,  S P Mayalarp,  J Butler,  S R McAdam,  C C O'Hare,  J A Hartley
Affiliations

Affiliation

  • 1 CRC Department of Biophysical Chemistry, Drug Development, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, U.K.
PMID: 9022802 DOI: 10.1021/jm960492j
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.

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