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.

Full Text

Duke Authors

Cited Authors

  • Dong, Q; Barsky, D; Colvin, ME; Melius, CF; Ludeman, SM; Moravek, JF; Colvin, OM; Bigner, DD; Modrich, P; Friedman, HS

Published Date

  • December 19, 1995

Published In

Volume / Issue

  • 92 / 26

Start / End Page

  • 12170 - 12174

PubMed ID

  • 8618865

Pubmed Central ID

  • PMC40318

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.92.26.12170


  • eng

Conference Location

  • United States