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

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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.