NDLI: Pt-based drugs: the spotlight will be on proteins

Content Provider	Royal Society of Chemistry (RSC)
Author	Sissi, C. Musetti, C. Pinato, O.
Copyright Year	2014
Abstract	Platinum-complexes represent some of the most successful groups of clinically used anticancer drugs. Their mechanism of action relies on the formation of stable DNA adducts occurring at the nitrogen in position 7 of guanine (N7) and involving one or two spatially close residues. The formation of stable DNA adducts is recognized as a DNA damaging event and, ultimately, drives cells to death. Nevertheless, nucleobases are not the only reliable targets of these drugs and other biomolecules can be involved. Among them large interest has been devoted to proteins since they contain several potential reactive sites for platinum (His, Met, and Cys) and, in particular, because the reaction of the metal with sulfur containing groups is a kinetically favored process. As a result, the occurrence of protein adducts and DNA–protein cross-links must be further taken into account in order to fully define cisplatin mechanism of action. Herein, we will summarize the most recent experimental evidence collected so far on protein–cisplatin adduct formation to better dissect its correlation with the drug pharmacological profile. Indeed, in addition to modulation of drug bioavailability and toxicity, the potential role of proteins as reaction intermediates or reservoir systems in platinum drugs can be envisaged. Additionally, the effects of Pt-coordinating groups on the chemical reactivity of the metal complexes will be reviewed. From all these outcomes a general model for Pt-based drugs mechanism of action can be drawn which is more articulate than the one currently supported. It claims proteins as reactive intermediates for DNA platination and it defines them as relevant to fully describe the clinical potential of this class of anticancer drugs.
Starting Page	380
Ending Page	395
Page Count	16
File Format	HTM / HTML PDF
ISSN	17565901
Volume Number	6
Issue Number	3
Journal	Metallomics
DOI	10.1039/c3mt00357d
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	DNA Bioavailability Nitrogen Sulfur N postcode area Guanine Protein Cisplatin Adduct Petroleum reservoir
Content Type	Text
Resource Type	Article
Subject	Chemistry Medicine Metals and Alloys Biochemistry Biomaterials Biophysics

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