3 research outputs found
Peculiar Features in the Crystal Structure of the Adduct Formed between <i>cis</i>-PtI<sub>2</sub>(NH<sub>3</sub>)<sub>2</sub> and Hen Egg White Lysozyme
The reactivity of <i>cis</i>-diamminediiodidoplatinum(II), <i>cis</i>-PtI<sub>2</sub>(NH<sub>3</sub>)<sub>2</sub>, the iodo analogue of cisplatin, with
hen egg white lysozyme (HEWL) was investigated by electrospray ionization
mass spectrometry and X-ray crystallography. Interestingly, the study
compound forms a stable 1:1 protein adduct for which the crystal structure
was solved at 1.99 Å resolution. In this adduct, the Pt<sup>II</sup> center, upon release of one ammonia ligand, selectively coordinates
to the imidazole of His15. Both iodide ligands remain bound to platinum,
with this being a highly peculiar and unexpected feature. Notably,
two equivalent modes of Pt<sup>II</sup> binding are possible that
differ only in the location of I atoms with respect to ND1 of His15.
The structure of the adduct was compared with that of HEWL–cisplatin,
previously described; differences are stressed and their important
mechanistic implications discussed
Interactions between Anticancer <i>trans</i>-Platinum Compounds and Proteins: Crystal Structures and ESI-MS Spectra of Two Protein Adducts of <i>trans</i>-(Dimethylamino)(methylamino)dichloridoplatinum(II)
The adducts formed between <i>trans</i>-(dimethylamino)(methylamino)dichloridoplatinum(II),
[t-PtCl<sub>2</sub>(dma)(ma)], and two model proteins, i.e., hen egg
white lysozyme and bovine pancreatic ribonuclease, were independently
characterized by X-ray crystallography and electrospray ionization
mass spectrometry. In these adducts, the Pt<sup>II</sup> center, upon
chloride release, coordinates either to histidine or aspartic acid
residues while both alkylamino ligands remain bound to the metal.
Comparison with the cisplatin derivatives of the same proteins highlights
for [t-PtCl<sub>2</sub>(dma)(ma)] a kind of biomolecular metalation
remarkably different from that of cisplatin
Auranofin, Et<sub>3</sub>PAuCl, and Et<sub>3</sub>PAuI Are Highly Cytotoxic on Colorectal Cancer Cells: A Chemical and Biological Study
The
solution behavior of auranofin, Et<sub>3</sub>PAuCl and
Et<sub>3</sub>PAuI, as well as their interactions with hen egg white
lysozyme, single strand oligonucleotide, and ds-DNA were comparatively
analyzed through NMR spectroscopy, ESI-MS, ethidium bromide displacement,
DNA melting and viscometric tests. The cytotoxic effects toward representative
colorectal cancer cell lines were found to be strong and similar in
the three cases and a good correlation could be established between
the cytotoxicity and the ability to inhibit thioredoxin reductase;
remarkably, <i>in vivo</i> acute toxicity experiments for
Et<sub>3</sub>PAuI confirmed that, similarly to auranofin, this drug
is well tolerated in a murine model. Overall, a very similar profile
emerges for Et<sub>3</sub>PAuI and Et<sub>3</sub>PAuCl, which retain
the potent cytotoxic effects of auranofin while showing some peculiar
features. These results demonstrate that the presence of the thiosugar
moiety is not mandatory for the pharmacological action, suggesting
that the tuning of some relevant chemical properties such as lipophilicity
could be exploited to improve bioavailability, with no loss of the
pharmacological effects