The binding modes of a rationally designed photoactivated DNA nuclease determined by NMR.

TitleThe binding modes of a rationally designed photoactivated DNA nuclease determined by NMR.
Publication TypeJournal Article
Year of Publication1995
JournalNucleic acids research
Volume23
Issue9
Pagination1576-83
Date Published1995 May 11
ISSN0305-1048
AbstractThe complex between the rationally designed synthetic DNA cleaving agent netropsin-diazene and the double-stranded DNA oligomer 5'-CGCAAAGGC-3'.5'-GCCTTTTGCG-3' was characterized by two-dimensional NMR spectroscopy in solution. Photolysis of netropsin-diazene bound to DNA generates a trimethylenemethane diradical intermediate that induces single-strand breaks in the DNA. The pi-diyl trimethylenemethane based compounds are a new class of DNA nucleases. We tested the following design criteria: (i) binding of the diazene and subsequent reactive diyl to the DNA, (ii) sequence selectivity in the ligand binding and (iii) prevention of diyl dimerization. Sixteen NOE derived ligand-DNA distance restraints were used to obtain the energy minimized model of the complex. The ligand is bound to the minor groove of the oligomer with the diazene at the 5' end of the A-tract in the predominant conformation of the complex. This form of the complex exchanges with a minor conformation in which the ligand is in the opposite orientation. The DNA maintains a B-form structure. Netropsin-diazene has fulfilled all of the design criteria, binding to the DNA duplex studied in the minor groove of the central AAAA tract in a 1:1 mode, preventing diyl dimerization and other side reactions from occurring.
PubMed Linkhttp://www.ncbi.nlm.nih.gov/pubmed/7784213?dopt=Abstract
Short TitleNucleic Acids Res