The anticancer drug cisplatin (cis-diamminedichloroplatinum-II) and related Pt(II) compounds form exchange-inert complexes with nucleic acids and other biomolecules. To better understand the range of cellular interactions available to these compounds, robust methods to track and analyze Pt-bound species are needed. A bioorthogonally reactive handle on a platinum ligand would allow for post-treatment covalent modification, streamlining separation, purification, and subsequent identification of platinum-bound species. To this end we have designed and synthesized a family of azide-containing platinum-pyridine derivatives capable of undergoing an azide-alkyne cycloaddition 'click' reaction with functionalized alkynes. These new platinum complexes have been characterized via 1H, 13C, and 195Pt NMR spectroscopy, and their respective nucleic acid binding capacities have been determined. Nucleic acids containing the new azide-derivatized Pt(II) compounds react selectively via click reaction with alkyne-modified fluorophores. Current work is focused on optimizing this system for further in vitro and in vivo analyses of Pt(II)-bound species.

Azide-containing Pt(II) derivatives for biomolecule analysis by Click chemistry

245th National Meeting (2013)

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