MECHANISM AND KINETICS OF OXIDATION OF GUANOSINE DERIVATIVES BY PT(IV) COMPLEXES

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来源获得了主要资金，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。铂化合物由于其抗癌活性而在生物学上是重要的。最广泛使用的铂类药物是顺铂，其铂的氧化态为+2。某些铂化合物的铂氧化态为+4，Pt（IV），对顺铂耐药的肿瘤有毒性。它们具有开发为口服活性抗癌药物的潜力。本实验室利用HPLC、NMR、UV/维斯和循环伏安法研究了Pt（IV）化合物与DNA的反应，探讨了Pt（IV）化合物的抗癌机理。我们发现一些Pt（IV）化合物将5 '-dGMP氧化为8-氧代-dGMP。它们还氧化寡聚体中的3 '-dGMP和5' G。我们计划研究DNA的氧化是否发生在体内。这些结果将增强我们对过渡金属/DNA化学的基础知识，并可能导致改进铂化疗药物的开发。

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. Platinum compounds are biologically important due to their anticancer activity. The most widely used platinum drug is cisplatin which has platinum in the oxidation state of +2. Some platinum compounds which has platinum in the oxidation state of +4, Pt(IV), are toxic to tumors which are resistant to cisplatin. And they have potential to be developed as orally active anticancer drugs. Our lab investigates the anticancer mechanism of Pt(IV) compounds by studying the reaction of Pt(IV) compounds and DNA using HPLC, NMR, UV/Vis, and Cyclic voltametry. We discovered that some Pt(IV) compounds oxidize 5'-dGMP to 8-oxo-dGMP. They also oxidize 3'-dGMP and 5'G in the oligomer. We plan to investigate if the oxidation of DNA occurs in the vivo. The results will enhance our basic knowledge of transition metal/DNA chemistry and could lead to the development of improved platinum chemotherapeutic drugs.