In-cell imaging of inorganic compounds is a challenging problem. Platinum anticancer compounds are used worldwide as antitumor agents. Despite broad use, a comprehensive description of molecular targets and cellular localization is not available for these reagents. Due to their small size and sensitivity to modification, platinum compounds provide challenges for in-cell localization by sensitive fluorescence microscopy methods. In order to visualize and isolate targets of these reagents, we have modified platinum compounds for post-treatment ‘click’ azide-alkyne cycloaddition reactions. Using this approach, post-treatment fluorescent labeling of mammalian cell cultures demonstrates distinct and time-dependent accumulation of Pt compounds in the nucleus and nucleolus. To enhance sensitivity and resolution for cell imaging, additional secondary labeling methods have been developed. A comparison of several Pt reagents and partner fluorescent dyes modified for click chemistry will be presented. Financial support by the National Science Foundation NSF CHE-1413677 is gratefully acknowledged. 1. Hostetter AA, Osborn MF, DeRose VJ (2012) ACS Chem. Biol. 7:218-225. 2. Osborn MF, White JN, DeRose VJ (2014) ACS Chem. Biol. 9: 2404–2411. 3. White JN, Osborn MF, Moghaddam AN, Guzman LE, Haley MM, DeRose VJ (2013) J. Am. Chem. Soc. 135: 11680-11683. 4. White, JD, Guzman LE, Zakharov LN, Haley MM, DeRose VJ (2015) Angew. Chem. 54: 1032-1035. 5. Moghaddam, AD, White, JD, Cunningham, RM, Loes, AN, Haley, MM, DeRose, VJ (2015) Dalton Trans. 44: 3536-3539.

In-cell fluorescence imaging of platinum anticancer compounds detected using click chemistry

251st National Meeting (2016)

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