{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Salerno D"],"funding":["Ministero dell’Istruzione, dell’Università e della Ricerca","Università degli Studi di Milano-Bicocca"],"pagination":["2151-61"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4880801"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["110(10)"],"pubmed_abstract":["Platinum-containing molecules are widely used as anticancer drugs. These molecules exert cytotoxic effects by binding to DNA through various mechanisms. The binding between DNA and platinum-based drugs hinders the opening of DNA, and therefore, DNA duplication and transcription are severely hampered. Overall, impeding the above-mentioned important DNA mechanisms results in irreversible DNA damage and the induction of apoptosis. Several molecules, including multinuclear platinum compounds, belong to the family of platinum drugs, and there is a body of research devoted to developing more efficient and less toxic versions of these compounds. In this study, we combined different biophysical methods, including single-molecule assays (magnetic tweezers) and bulk experiments (ultraviolet absorption for thermal denaturation) to analyze the differential stability of double-stranded DNA in complex with either cisplatin or multinuclear platinum agents. Specifically, we analyzed how the binding of BBR3005 and BBR3464, two representative multinuclear platinum-based compounds, to DNA affects its stability as compared with cisplatin binding. Our results suggest that single-molecule approaches can provide insights into the drug-DNA interactions that underlie drug potency and provide information that is complementary to that generated from bulk analysis; thus, single-molecule approaches have the potential to facilitate the selection and design of optimized drug compounds. In particular, relevant differences in DNA stability at the single-molecule level are demonstrated by analyzing nanomechanically induced DNA denaturation. On the basis of the comparison between the single-molecule and bulk analyses, we suggest that transplatinated drugs are able to locally destabilize small portions of the DNA chain, whereas other regions are stabilized."],"journal":["Biophysical journal"],"pubmed_title":["Platinum-Based Drugs and DNA Interactions Studied by Single-Molecule and Bulk Measurements."],"pmcid":["PMC4880801"],"funding_grant_id":["2010LKE4CC"],"pubmed_authors":["Brioschi S","Missana N","Salerno D","Zaffaroni N","Beretta GL","Cassina V","Mantegazza F","Nardo L","Bellini T","Cristofalo M","Tempestini A","Giovannoni R","Zanchetta G","Cerrito MG"],"additional_accession":[]},"is_claimable":false,"name":"Platinum-Based Drugs and DNA Interactions Studied by Single-Molecule and Bulk Measurements.","description":"Platinum-containing molecules are widely used as anticancer drugs. These molecules exert cytotoxic effects by binding to DNA through various mechanisms. The binding between DNA and platinum-based drugs hinders the opening of DNA, and therefore, DNA duplication and transcription are severely hampered. Overall, impeding the above-mentioned important DNA mechanisms results in irreversible DNA damage and the induction of apoptosis. Several molecules, including multinuclear platinum compounds, belong to the family of platinum drugs, and there is a body of research devoted to developing more efficient and less toxic versions of these compounds. In this study, we combined different biophysical methods, including single-molecule assays (magnetic tweezers) and bulk experiments (ultraviolet absorption for thermal denaturation) to analyze the differential stability of double-stranded DNA in complex with either cisplatin or multinuclear platinum agents. Specifically, we analyzed how the binding of BBR3005 and BBR3464, two representative multinuclear platinum-based compounds, to DNA affects its stability as compared with cisplatin binding. Our results suggest that single-molecule approaches can provide insights into the drug-DNA interactions that underlie drug potency and provide information that is complementary to that generated from bulk analysis; thus, single-molecule approaches have the potential to facilitate the selection and design of optimized drug compounds. In particular, relevant differences in DNA stability at the single-molecule level are demonstrated by analyzing nanomechanically induced DNA denaturation. On the basis of the comparison between the single-molecule and bulk analyses, we suggest that transplatinated drugs are able to locally destabilize small portions of the DNA chain, whereas other regions are stabilized.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 May","modification":"2025-05-18T13:45:31.602Z","creation":"2025-05-18T13:45:31.602Z"},"accession":"S-EPMC4880801","cross_references":{"pubmed":["27224480"],"doi":["10.1016/j.bpj.2016.02.030"]}}