Affiliation:
1. Department of Chemistry Ugo Schiff, University of Florence, Sesto Fiorentino, Firenze, Italy
2. Department of Chemical Sciences, University of Naples Federico II, Napoli, Italy
Abstract
Pt-based drugs are widely used in clinics for the treatment of cancer. The mechanism of action
of these molecules relies 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, are 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 occur
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 metallated protein structures, Pt centers coordinate few protein
side chains, such as His, Met, Cys, Asp, Glu and Lys residues upon releasing labile ligands.
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,General Medicine
Reference85 articles.
1. Kelland L.; The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer 2007,7(8),573-584
2. Robillard M.S.; Reedijk J.; Platinum bbased anticancer drugsbased in part on the article platinum based anticancer drugs by Steven J. Brown, Christine S. Chow & Stephen J. Lippard which appeared in the encyclopedia of inorganic chemistry, First Edition .In: Encyclopedia of Inorganic and Bioinorganic Chemistry; John Wiley
3. Sherman S.E.; Gibson D.; Wang A.H.; Lippard S.J.; X-ray structure of the major adduct of the anticancer drug cisplatin with DNA: cis-.[Pt(NH3)2(d(pGpG)) Science 1985,230(4724),412-417
4. Zamble D.B.; Mu D.; Reardon J.T.; Sancar A.; Lippard S.J.; Repair of cisplatin--DNA adducts by the mammalian excision nuclease. Biochemistry 1996,35(31),10004-10013
5. Jung Y.; Lippard S.J.; Direct cellular responses to platinum-induced DNA damage. Chem Rev 2007,107(5),1387-1407
Cited by
13 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献