[D(CGCGAATTCGCG)]2 IN THE PRESENCE OF PLATINUM ANTICANCER DRUG

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。铂类抗癌药物顺铂的主要缺点是严重的副作用和获得性耐药性，这不可避免地增加了患者的药物剂量。因此，迫切需要一种新的基于铂的抗癌药物来避免这些临床不便，以改善患者的生活质量（QOL）。通常认为，顺铂的抗癌作用是通过在DNA上形成1，2-链内交联而引发的，导致严重的DNA扭曲。然而，大多数结构相关的顺铂类似物显示出对顺铂的交叉耐药性，这可能是由于它们具有相似的生物学后果。因此，我们建立了双链DNA [d（CGCGAATTCGCG）]2在各种铂基抗癌药物存在下结晶的晶体学研究。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The major drawbacks of the platinum based anticancer drug, cisplatin, are the serious side effects and acquired drug-resistance, which inevitably increases the drug dosage to patients. Accordingly, a new platinum based anticancer drug that circumvents these clinical inconveniences is strongly desired to improve patient¿¿¿s quality of life (QOL). It is generally believed that cisplatin¿¿¿s anticancer action is triggered by formation of 1,2-intrastrand crosslinks on DNA, resulting in a severe DNA distortion. Most of the structurally related cisplatin-analogues, however, show cross-resistance to cisplatin, probably due to their similar biological consequences. Therefore, we have set up a crystallographic study on a double-stranded DNA, [d(CGCGAATTCGCG)]2, crystallized in the presence of various platinum-based anticancer dr