Tryptophan switch for a photoactivated platinum anticancer complex

Jennifer S. Butler, Julie A. Woods, Nicola J. Farrer, Mark E. Newton, Peter J. Sadler

    Research output: Contribution to journalArticle

    80 Citations (Scopus)

    Abstract

    The octahedral PtIV complex trans,trans,trans-[Pt(N3)2(OH)2(py)2] (1) is potently cytotoxic to cancer cells when irradiated with visible (blue) light. We show that the acute photocytotoxicity can be switched off by low doses (500 µM) of the amino acid L-tryptophan. EPR and NMR spectroscopic experiments using spin traps show that L-Trp quenches formation of azidyl radicals, probably acting as an electron donor. L-Trp is well known as a mediator of electron transfer between distant electron-acceptor/donor centers in proteins and such properties may make the free amino acid clinically useful for controlling the activity of photochemotherapeutic azido PtIV drugs. Since previous work has demonstrated the ability of photoactivated 1 to platinate DNA, this suggests that the high potency of such photoactive platinum complexes is related to their dual attack on cancer cells by radicals and PtII photoproducts.
    Original languageEnglish
    Pages (from-to)16508-16511
    Number of pages4
    JournalJournal of the American Chemical Society
    Volume134
    Issue number40
    DOIs
    Publication statusPublished - 10 Oct 2012

    Fingerprint Dive into the research topics of 'Tryptophan switch for a photoactivated platinum anticancer complex'. Together they form a unique fingerprint.

  • Cite this

    Butler, J. S., Woods, J. A., Farrer, N. J., Newton, M. E., & Sadler, P. J. (2012). Tryptophan switch for a photoactivated platinum anticancer complex. Journal of the American Chemical Society, 134(40), 16508-16511. https://doi.org/10.1021/ja3074159