New Pt(II) Complexes for the Investigation of Copper-Mediated Degradation in Pt-Bound RNA Click Reactions

Presenter: Lindsay Guzman

Mentor: Victoria DeRose

Oral Presentation

Major: Chemistry

RNAs contribute to a wide range of essential biological processes such as protein function, catalysis, transcriptional and translational regulation. Small-molecule binders, such as the platinum(II) anticancer drug cisplatin, can be used to probe cellular RNA structures and functions. We are focusing on the functionalization of Pt complexes with azide and alkyne moieties that may allow for the subsequent purification and high-throughput sequencing of Pt-RNA adducts in the copper-catalyzed Huisgen cycloaddition (click) reaction. The click reaction involves the formation of a thermodynamically stable five-membered ring between an azide and alkyne in the presence of a Cu catalyst. Because of the reactive nature of the necessary Cu catalyst, it is speculated that Cu is facilitating observed RNA degradation in model reactions, thus lowering the efficiency and usefulness of the post-treatment click modifications. Three new Pt(II) complexes that vary in linker length from the platinum center to the copper-catalyzed click reaction site will be synthesized to probe the possible influence of click-mediated Cu recruitment on cleavage of the oligonucleotide, which will be determined by gel chromatography. This will allow for further investigation of additional and undesired copper-mediated reactivity as well as improved yield of Pt-bound RNA click reactions, which will help elucidate the biological processes of RNA.

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