Yao S, Murali D, Seetharamulu P, Haridas K, Petluru P N, Reddy D G, Hausheer F H
BioNumerik Pharmaceuticals Inc., San Antonio, Texas 78229, USA.
Cancer Res. 1998 Sep 1;58(17):3782-6.
We report the first experimental observation that a clinically important camptothecin [CPT; topotecan (TPT), a water-soluble CPT] binds directly and noncovalently to double-stranded DNA and single-stranded DNA structures in the absence of topoisomerase I, but only in the lactone form. We observed clear DNA sequence specificity of the TPT lactone binding to duplex DNA, which was comprised of alternating purine-pyrimidine sequences that contained dT. These structural studies of direct TPT lactone-DNA binding support several important considerations involving possible mechanism(s) of anticancer activity of CPT-type drugs containing a 20(S) lactone moiety.
一种具有临床重要性的喜树碱[CPT；拓扑替康（TPT），一种水溶性CPT]在不存在拓扑异构酶I的情况下，仅以内酯形式直接且非共价地结合双链DNA和单链DNA结构。我们观察到TPT内酯与双链DNA的结合具有明确的DNA序列特异性，该双链DNA由包含dT的交替嘌呤 - 嘧啶序列组成。这些关于TPT内酯与DNA直接结合的结构研究支持了几个重要的考虑因素，涉及含20(S)内酯部分的CPT类药物抗癌活性的可能机制。
