Most cited article - PubMed ID 38727007
Picoplatin binding to proteins: X-ray structures and mass spectrometry data on the adducts with lysozyme and ribonuclease A
Here we investigated cytotoxicity and DNA and protein binding of an iodido analog of picoplatin, the cis-ammine-diiodido(2-methylpyridine)platinum(II) complex (I-picoplatin). I-picoplatin (IC50 = 3.7-12.4 μM) outperforms picoplatin (IC50 = 11.8-22.6 μM) in the human cancer cell lines used and shows a greater ability to overcome the cisplatin resistance of A2780 ovarian cancer cells than does picoplatin. I-picoplatin also induces different cell cycle changes (reduced S-phase fraction and an increase in the G2/M phase arrest) in HeLa cervical carcinoma cells compared to both picoplatin and cisplatin. Binding of the metal compound to DNA model systems was investigated by ethidium bromide displacement assay and circular dichroism. Its reactivity with lysozyme (HEWL) and pancreatic RNase A was studied by X-ray diffraction and mass spectrometry experiments. I-picoplatin binds the DNA double helix and is able to retain the 2-methylpyridine ligand and at least one of the two iodido ligands when bound to the two proteins. Various Pt-containing moieties, including one based on the isomerized structure of I-picoplatin, coordinate the His and Met residues. A low-resolution structure of the I-picoplatin/human serum albumin (HSA) adduct has also been solved. The side chains of His146, Met289, and Met329 are the primary binding sites of the I-picoplatin moieties on HSA.
- MeSH
- DNA * metabolism chemistry MeSH
- Humans MeSH
- Serum Albumin, Human * metabolism chemistry MeSH
- Molecular Structure MeSH
- Muramidase * metabolism chemistry MeSH
- Cell Line, Tumor MeSH
- Organoplatinum Compounds * chemistry pharmacology chemical synthesis metabolism MeSH
- Ribonuclease, Pancreatic * metabolism chemistry MeSH
- Cell Proliferation drug effects MeSH
- Antineoplastic Agents * pharmacology chemistry chemical synthesis metabolism MeSH
- Drug Screening Assays, Antitumor MeSH
- Protein Binding MeSH
- Binding Sites MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- DNA * MeSH
- Serum Albumin, Human * MeSH
- Muramidase * MeSH
- Organoplatinum Compounds * MeSH
- Ribonuclease, Pancreatic * MeSH
- Antineoplastic Agents * MeSH
