Ligand effects on the binding of cis- and trans-[PtCl2Am1Am2] to proteins

Abstract

As part of a systematic study of the basic principles that govern the formation and reactivity of Pt-protein adducts, we report the effect of substituting the amine ligand of cis- and trans-[PtCl(2)(NH(3))(2)] complexes with bulkier planar aromatic or nonplanar cyclic amine ligands on the binding properties of the complexes to ubiquitin and to horse heart myoglobin. The ligand replacement had a different effect on the cis or trans isomers investigated. In the cis-Pt complexes, replacing one or both amine ligands by piperidine or 4-picoline dramatically decreased the binding of the complexes to the proteins studied, whereas in the substituted trans-Pt complexes replacement of the amine by a piperidine or 4-picoline increased the binding rate. This behavior may have to do with the different preferred binding sites of the cis- and trans-Pt complexes. The bulkier cis- or trans-Pt complexes investigated also did not display a preference for Met1 of ubiquitin, possibly owing to steric constraints imposed by the substituted ligands. The introduction of a charged piperazine ligand significantly decreased the rate of binding to the protein, possibly owing to electrostatic interactions or hydrogen-bond formations with the surface of the protein. The binding of the complexes to ubiquitin and myoglobin does not disrupt the folding of the proteins as judged by electrospray ionization mass spectrometry.

Water soluble cationic trans-platinum complexes which induce programmed cell death in the protozoan parasite Leishmania infantum

“…PI is a DNA intercalator that passes through the cell membrane and goes to the nucleus when the cell membrane integrity has been lost. So, in a typical annexin V-PI scattergram the annexinV À /PI À cell population (left bottom quadrant) contains alive cells, the annexinV + /PI À cell population (right bottom quadrant) contains cells experiencing early PCD, the annexinV + /PI + cell population (right upper quadrant) contains cells undergoing late PCD, and finally, the annexinV À /PI + cell population (left upper quadrant) contains necrotic cells [19]. Fig.…”

“…1. The synthetic methods leading to the synthesis of compounds 1-4 are based on the trans effect of Pt(II) complexes so that the trans geometry of the synthesized compounds is guaranteed [19]. These compounds exhibit a good water solubility having a limit of solubility of 1 mg/mL.…”

Preparation, cytotoxicity and interactions with nucleophiles of three isomeric transplatinum complexes containing methylpiperidine ligands

“…In a more recent study we reported that for trans compounds such as trans-[PtCl 2 (NH 3 )(Am)], where Am = 4-picoline and piperidine, substitution of one small ammine ligand of transplatin with either bulky planar aromatic or with non-planar heterocyclic amines does not decrease the binding rate of the divalent Pt complex to the protein [19]. The 1:1 platination reactions of ubiquitin with 1-2 mM of platinum complexes I-III, at 37°C, were monitored by ESIMS.…”

Investigation of interaction between human hemoglobin A0 and platinum anticancer drugs by capillary isoelectric focusing with whole column imaging detection

“…A recent review summarizes the progress made in the applications of modern analytical methodologies for antitumor metallodrug-protein studies [20]. ESI-MS was recently shown as an extremely useful tool for studying the cisplatin-protein interactions [19,[21][22][23][24][25]. Also, HPLC [19,24,[26][27][28] and a complementary high-resolution technique with an orthogonal separation mechanism, CE [29][30][31], are growing in importance for characterizing the protein binding for different metal complexes.…”