A structural basis for a phosphoramide mustard-induced DNA interstrand cross-link at 5'-d(GAC).
Journal Article (Journal Article)
Phosphoramide mustard-induced DNA interstrand cross-links were studied both in vitro and by computer simulation. The local determinants for the formation of phosphoramide mustard-induced DNA interstrand cross-links were defined by using different pairs of synthetic oligonucleotide duplexes, each of which contained a single potentially cross-linkable site. Phosphoramide mustard was found to cross-link dG to dG at a 5'-d(GAC)-3'. The structural basis for the formation of this 1,3 cross-link was studied by molecular dynamics and quantum chemistry. Molecular dynamics indicated that the geometrical proximity of the binding sites also favored a 1,3 dG-to-dG linkage over a 1,2 dG-to-dG linkage in a 5'-d(GCC)-3' sequence. While the enthalpies of 1,2 and 1,3 mustard cross-linked DNA were found to be very close, a 1,3 structure was more flexible and may therefore be in a considerably higher entropic state.
- Dong, Q; Barsky, D; Colvin, ME; Melius, CF; Ludeman, SM; Moravek, JF; Colvin, OM; Bigner, DD; Modrich, P; Friedman, HS
- December 19, 1995
Volume / Issue
- 92 / 26
Start / End Page
- 12170 - 12174
Pubmed Central ID
International Standard Serial Number (ISSN)
Digital Object Identifier (DOI)
- United States