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

2.50
Hdl Handle:
http://hdl.handle.net/10541/95491
Title:
Cross-linking and sequence specific alkylation of DNA by aziridinyl quinones. 2. Structure requirements for sequence selectivity.
Authors:
Hargreaves, Robert H J; Mayalarp, Stephen P; Butler, John; McAdam, S R; O'Hare, C C; Hartley, John A
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.
Affiliation:
CRC Department of Biophysical Chemistry, Drug Development, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, U.K.
Citation:
Cross-linking and sequence specific alkylation of DNA by aziridinyl quinones. 2. Structure requirements for sequence selectivity. 1997, 40 (3):357-61 J. Med. Chem.
Journal:
Journal of Medicinal Chemistry
Issue Date:
31-Jan-1997
URI:
http://hdl.handle.net/10541/95491
DOI:
10.1021/jm960492j
PubMed ID:
9022802
Type:
Article
Language:
en
ISSN:
0022-2623
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorHargreaves, Robert H Jen
dc.contributor.authorMayalarp, Stephen Pen
dc.contributor.authorButler, Johnen
dc.contributor.authorMcAdam, S Ren
dc.contributor.authorO'Hare, C Cen
dc.contributor.authorHartley, John Aen
dc.date.accessioned2010-04-01T14:22:35Z-
dc.date.available2010-04-01T14:22:35Z-
dc.date.issued1997-01-31-
dc.identifier.citationCross-linking and sequence specific alkylation of DNA by aziridinyl quinones. 2. Structure requirements for sequence selectivity. 1997, 40 (3):357-61 J. Med. Chem.en
dc.identifier.issn0022-2623-
dc.identifier.pmid9022802-
dc.identifier.doi10.1021/jm960492j-
dc.identifier.urihttp://hdl.handle.net/10541/95491-
dc.description.abstractThe 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.en
dc.language.isoenen
dc.subjectCultured Tumour Cellsen
dc.subject.meshAlkylation-
dc.subject.meshAntineoplastic Agents, Alkylating-
dc.subject.meshAziridines-
dc.subject.meshBenzoquinones-
dc.subject.meshCell Survival-
dc.subject.meshComputer Simulation-
dc.subject.meshCross-Linking Reagents-
dc.subject.meshDNA-
dc.subject.meshElectrophoresis, Polyacrylamide Gel-
dc.subject.meshGuanine-
dc.subject.meshHumans-
dc.subject.meshMagnetic Resonance Spectroscopy-
dc.subject.meshMass Spectrometry-
dc.subject.meshModels, Molecular-
dc.subject.meshNucleic Acid Conformation-
dc.subject.meshTumor Cells, Cultured-
dc.titleCross-linking and sequence specific alkylation of DNA by aziridinyl quinones. 2. Structure requirements for sequence selectivity.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Biophysical Chemistry, Drug Development, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, U.K.en
dc.identifier.journalJournal of Medicinal Chemistryen

Related articles on PubMed

All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.