Dong Q, Barsky D, Colvin M E, Melius C F, Ludeman S M, Moravek J F, Colvin O M, Bigner D D, Modrich P, Friedman H S
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12170-4. doi: 10.1073/pnas.92.26.12170.
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.
研究了磷酰胺芥诱导的DNA链间交联，包括体外研究和计算机模拟。通过使用不同对的合成寡核苷酸双链体来确定磷酰胺芥诱导DNA链间交联形成的局部决定因素，每对双链体都包含一个单一的潜在可交联位点。发现磷酰胺芥在5'-d(GAC)-3'处使dG与dG交联。通过分子动力学和量子化学研究了这种1,3交联形成的结构基础。分子动力学表明，在5'-d(GCC)-3'序列中，结合位点的几何接近性也有利于形成1,3 dG-to-dG连接，而不是1,2 dG-to-dG连接。虽然发现1,2和1,3芥酸交联DNA的焓非常接近，但1,3结构更灵活，因此可能处于相当高的熵状态。
