Abstract:
:Platinum(IV) complexes generally require reduction to reactive Pt(II) species to exert their chemotherapeutic activity. The process of reductive activation of (15)N-labeled (OC-6-43)-bis(acetato)diamminedichloridoplatinum(IV), in the presence of nicotinamide adenine dinucleotide (NADH) and horse heart cytochrome c (cyt c), was monitored by (1)H,(15)N-HSQC NMR spectroscopy and protein digestion experiments. It has been shown that cyt c plays a catalytic role in the transfer of two reducing equivalents from NADH to Pt(IV) species. Noncovalent interactions between reduced monoaqua cisplatin (cis-[PtCl((15)NH3)2(H2O)](+)) and the protein, in the proximity of the heme cofactor, and also covalent binding of platinum to the protein region around Met65 and Met80 take place.
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Lasorsa A,Stuchlíková O,Brabec V,Natile G,Arnesano Fdoi
10.1021/acs.molpharmaceut.6b00438subject
Has Abstractpub_date
2016-09-06 00:00:00pages
3216-23issue
9eissn
1543-8384issn
1543-8392pii
10.1021/acs.molpharmaceut.6b00438journal_volume
13pub_type
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