title: Tryptophan switch for a photoactivated platinum anticancer complex.
abstract: The octahedral Pt(IV) complex trans,trans,trans-[Pt(N(3))(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 the formation of azidyl radicals, probably by 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 Pt(IV) 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 Pt(II) photoproducts.
authors.affiliation: Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Butler
authors.forename: Julie A
authors.initials: JA
authors.lastname: Woods
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Farrer
authors.forename: Mark E
authors.initials: ME
authors.lastname: Newton
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sadler
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D008027:Light; D008958:Models, Molecular; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D014364:Tryptophan / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D017319:Photosensitizing Agents; D014364:Tryptophan