{"corpus_id":43461930,"paper_sha":"166364ce22ec112e150c962be91a3aa98b59391c","doi":"10.1021/JM050902G","arxiv_id":null,"pmid":16366602,"pmcid":"PMC2522373","mag_id":2152195319,"dblp_id":null,"acl_id":null,"title":"A new bisintercalating anthracycline with picomolar DNA binding affinity.","year":2005,"publication_date":"2005-12-29","venue":"Journal of Medicinal Chemistry","journal":{"name":"Journal of medicinal chemistry","pages":"\n          8209-19\n        ","volume":"48 26"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle","Study"],"pubmed_pub_types":["Comparative Study","Journal Article","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Medicine","Chemistry"],"reference_count":42,"citation_count":56,"influential_citation_count":0,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Calorimetry, Differential Scanning","mj":false,"ui":"D002152"},{"d":"DNA","mj":false,"qs":[{"q":"chemistry","mj":true,"ui":"Q000737"},{"q":"radiation effects","mj":false,"ui":"Q000528"}],"ui":"D004247"},{"d":"Daunorubicin","mj":false,"qs":[{"q":"analogs & derivatives","mj":true,"ui":"Q000031"},{"q":"chemical synthesis","mj":false,"ui":"Q000138"},{"q":"chemistry","mj":false,"ui":"Q000737"},{"q":"pharmacology","mj":false,"ui":"Q000494"}],"ui":"D003630"},{"d":"Drug Design","mj":false,"ui":"D015195"},{"d":"Fishes","mj":false,"ui":"D005399"},{"d":"Flow Cytometry","mj":false,"ui":"D005434"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Intercalating Agents","mj":false,"qs":[{"q":"chemical synthesis","mj":true,"ui":"Q000138"},{"q":"chemistry","mj":false,"ui":"Q000737"},{"q":"pharmacology","mj":false,"ui":"Q000494"}],"ui":"D007364"},{"d":"Jurkat Cells","mj":false,"qs":[{"q":"drug effects","mj":false,"ui":"Q000187"}],"ui":"D019169"},{"d":"Male","mj":false,"ui":"D008297"},{"d":"Models, Molecular","mj":false,"ui":"D008958"},{"d":"Spermatozoa","mj":false,"qs":[{"q":"chemistry","mj":false,"ui":"Q000737"}],"ui":"D013094"},{"d":"Thermodynamics","mj":false,"ui":"D013816"},{"d":"Ultraviolet Rays","mj":false,"ui":"D014466"}],"chemicals":[{"n":"Intercalating Agents","ui":"D007364","reg":"0"},{"n":"WP 631","ui":"C104426","reg":"0"},{"n":"WP 762","ui":"C507405","reg":"0"},{"n":"DNA","ui":"D004247","reg":"9007-49-2"},{"n":"Daunorubicin","ui":"D003630","reg":"ZS7284E0ZP"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://figshare.com/articles/journal_contribution/A_New_Bisintercalating_Anthracycline_with_Picomolar_DNA_Binding_Affinity/3249478/1/files/5084296.pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/166364ce22ec112e150c962be91a3aa98b59391c","s2_open_access_license":"CCBYNC","s2_open_access_status":"GREEN","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"A new bisintercalating anthracycline (WP762) has been designed, in which monomeric units of daunorubicin have been linked through their amino groups on the daunosamine moieties using an m-xylenyl linker. Differential scanning calorimetry and UV melting experiments were used to measure the ultratight binding of WP762 to DNA. The binding constant for the interaction of WP762 with herring sperm DNA was determined to be 7.3 (+/-0.2) x 10(12) M(-1) at 20 degrees C. The large favorable binding free energy of -17.3 kcal mol(-1) was found to result from a large negative enthalpic contribution of -33.8 kcal mol(-1) and an opposing entropic term (-TDeltaS = +16.5 kcal mol(-1)). A comparative molecular modeling study rationalized the increased binding by the m-xylenyl linker of WP762 positioning in the DNA minor groove compared to the p-xylenyl linker found in WP631, the first bis-anthracycline of this type. The cytotoxicity of WP762 was compared to that of other anthracyclines in Jurkat T lymphocytes. These studies, together with an analysis of the cell-cycle traverse in the presence of WP762, suggest that in these cells the new drug is more cytotoxic than the structurally related WP631.","claims":[{"public_id":"cl_5b3c7ccf378c774074e8e06be32ae222","status":"active","text":"The large favorable binding free energy of WP762 arises from a strong negative enthalpic contribution that is opposed by an unfavorable entropic term.","confidence":0.96,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_5b3c7ccf378c774074e8e06be32ae222"},{"public_id":"cl_e016295e39124eac2eeea16c7cba106c","status":"active","text":"The m-xylenyl linker in WP762 positions the drug in the DNA minor groove more effectively than the p-xylenyl linker in WP631.","confidence":0.93,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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