Sherman S E, Gibson D, Wang A H, Lippard S J
Science. 1985 Oct 25;230(4724):412-7. doi: 10.1126/science.4048939.
Crystals of the adduct of the anticancer drug cis-diamminedichloroplatinum(II), cis-DDP, with d(pGpG), its putative target on DNA in the cancer cell, have been obtained and used in an x-ray crystallographic study to elucidate the molecular structure to atomic resolution. Each of the four crystallographically independent cis-[Pt(NH3)2(d(pGpG))] molecules is comprised of a square-planar platinum atom bonded to two ammonia ligands and two N(7) atoms of guanosine nucleosides from the same chain. Base stacking of the two adjacent guanine rings is completely disrupted by coordination to the cis-(Pt(NH3)2)2+ unit. Comparison of the backbone and deoxyribose ring torsion angles with those found by previous (nuclear magnetic resonance spectroscopy) studies of this adduct in solution demonstrates that the solid state geometry is substantially the same as that in solution. The relevance of these results to the molecular mechanism of action of cis-DDP is discussed.
已获得抗癌药物顺二氯二氨铂（II）（cis-DDP）与d（pGpG）（其在癌细胞DNA上的假定靶点）的加合物晶体，并将其用于X射线晶体学研究，以阐明分子结构至原子分辨率。四个晶体学独立的顺式-[Pt(NH₃)₂(d(pGpG))]分子中的每一个都由一个平面正方形铂原子组成，该铂原子与两个氨配体以及来自同一条链的鸟苷核苷的两个N(7)原子相连。两个相邻鸟嘌呤环的碱基堆积通过与顺式-(Pt(NH₃)₂)²⁺单元配位而完全被破坏。将主链和脱氧核糖环扭转角与先前对该加合物在溶液中的（核磁共振光谱）研究结果进行比较表明，固态几何结构与溶液中的基本相同。讨论了这些结果与顺铂作用分子机制的相关性。
