Kohn K W, Hartley J A, Mattes W B
Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, MD.
Nucleic Acids Res. 1987 Dec 23;15(24):10531-49. doi: 10.1093/nar/15.24.10531.
Quantitative determinations were carried out of the relative reaction rates of several nitrogen mustards at various guanine-N7 positions in DNA fragments of known sequence. The findings suggest structural hypotheses of the origins of the reaction selectivities. End-labeled DNA fragments were reacted with nitrogen mustards, and the guanine-N7 alkylation sites were analyzed by gel electrophoresis. Relative reaction intensities were determined by computer analysis of digitized densitometer scans. The differences in reaction intensities at different G's were in part attributable to the effects of nearest neighbor base pairs on the molecular electrostatic potential near the reaction site. Uracil and quinacrine mustards have specific sequence preferences for reaction that differ from other mustards. The nature of the specific sequence preferences were determined and hypotheses are proposed to explain their origin.
对几种氮芥在已知序列的DNA片段中不同鸟嘌呤-N7位置的相对反应速率进行了定量测定。这些发现提示了反应选择性起源的结构假说。将末端标记的DNA片段与氮芥反应，通过凝胶电泳分析鸟嘌呤-N7烷基化位点。通过对数字化密度计扫描结果进行计算机分析来确定相对反应强度。不同鸟嘌呤处反应强度的差异部分归因于相邻碱基对对反应位点附近分子静电势的影响。尿嘧啶和喹吖因氮芥对反应具有特定的序列偏好，这与其他氮芥不同。确定了特定序列偏好的性质，并提出假说来解释其起源。
