Interaction of Platinum-based Drugs with Proteins: An Overview of Representative Crystallographic Studies.

Interaction of Platinum-based Drugs with Proteins: An Overview of Representative Crystallographic Studies. Curr Top Med Chem. 2020 Jun 24;: Authors: Ferraro G, Loreto D, Merlino A Abstract Pt-based drugs are widely used in clinics for the treatment of cancer. The mechanism of action of these molecules rely on their interaction with DNA. However, the recognition of these metal compounds by proteins plays an important role in defining pharmacokinetics, side effects and their overall pharmacological profiles. Single crystal X-ray diffraction studies provided important information on the molecular mechanisms at the basis of this process. Here, the molecular structures of representative adducts obtained upon reaction with proteins of selected Pt-based drugs, including cisplatin, carboplatin and oxaliplatin, were briefly described and comparatively examined. Data indicate that metal ligands play a significant role in driving the reaction of Pt compounds with proteins; non-covalent interactions that are formed in the early steps of Pt compound/protein recognition process play a crucial role in defining the structure of the final Pt-protein adduct. In the metalated protein structures, Pt centers coordinate few protein side chains, such as His, Met, Cys, Asp, Glu and Lys residues upon releasing of labile ligands. PMID: 32579504 [PubMed - as supplied by publisher]
Source: Current Topics in Medicinal Chemistry - Category: Chemistry Authors: Tags: Curr Top Med Chem Source Type: research