Poster abstracts
Poster number 60 submitted by Bett Kimutai
Reactivity and impact of amino-acid-linked platinum(II) analogues in RNA and DNA
Bett Kimutai (Department of Chemistry, Wayne State University, Detroit, MI 48202), Chenchen He (Department of Chemistry, Wayne State University, Detroit, MI 48202), M. T. Rodgers (Department of Chemistry, Wayne State University, Detroit, MI 48202), Christine S. Chow (Department of Chemistry, Wayne State University, Detroit, MI 48202)
Abstract:
RNA is a competitive target of cisplatin and is able to accumulate inert platinum adducts. Aquated cisplatin may have preferential target residues in RNA as observed with DNA. Cisplatin can also be modified in a number of ways with ligands of varied sizes, polarities, and charges. These features can affect the kinetics of interaction with RNA, the types of adducts formed, and the preferred sites of coordination. In this study, amino acids were reacted with platinum to form a series of cisplatin analogues. Further, kinetic studies showed that ornithine-linked platinum (OrnPt) and arginine-linked platinum (ArgPt) are reactive towards both RNA and DNA nucleosides but with different selectivities. The two amino acid complexes have selectivity towards A/dA residues, in contrast to cisplatin which targets dG. Inductively coupled plasma mass spectrometry (ICPMS) quantification reveals higher accumulation of OrnPt and ArgPt on RNA over DNA. ArgPt also forms platinum adducts with poly(A) RNA. Platination by amino-acid-linked platinum analogues at particular sites on the ribonucleosides (i.e., N1, N3, or N7) is found to have varying impacts on their glycosidic bond stabilities. Weak glycosidic bonds accelerate depurination and could ultimately contribute to cell cytotoxicity. Such adducts may affect the biological roles of RNA such as mRNA maturation and protein synthesis.
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