{"id":{"repo_id":"wfu","oai_identifier":"oai:wakespace.lib.wfu.edu:10339/14770"},"canonical_url":"https://search.dev.ndltd.org/etd/wfu/oai:wakespace.lib.wfu.edu:10339/14770","repository":{"repo_id":"wfu","name":"Wake Forest University","base_url":"https://wakespace.lib.wfu.edu/oai/request"},"display":{"title":"CHARACTERIZATION OF THE RNA BINDING MODE OF A PLATINUM-ACRIDINE AGENT","abstract":"Pt-ACRAMTU (ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea) is a DNA-targeted anticancer agent that shows activity in a broad range of solid tumor cell lines. Unlike the classical platinum-based cross-linking drugs, this agent produces its cytotoxic effect by two synergistic DNA binding mechanisms: monofunctional platination and intercalation of the acridine chromophore. The RNA binding of platinum drugs has been studied to a much lesser extent. Recently, the RNA interactions of platinum-containing drugs and drug conjugates have been reported. In the current study, an RNA hairpin has been generated through in vitro transcription and treated with Pt-ACRAMTU. Our goal was to determine if specific RNA structural motifs are susceptible to intercalator-driven platination. Acidic digestion assays in conjunction with liquid chromatography-electrospray mass spectrometry analysis (LC-ESMS) was used to determine the specific bases modified by platinum. In addition, the RNA conformational changes induced by ACRAMTU and PT-ACRAMTU were also analyzed by circular dichroism (CD) spectroscopy.","abstract_html":"Pt-ACRAMTU (ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea) is a DNA-targeted anticancer agent that shows activity in a broad range of solid tumor cell lines. Unlike the classical platinum-based cross-linking drugs, this agent produces its cytotoxic effect by two synergistic DNA binding mechanisms: monofunctional platination and intercalation of the acridine chromophore. The RNA binding of platinum drugs has been studied to a much lesser extent. Recently, the RNA interactions of platinum-containing drugs and drug conjugates have been reported. In the current study, an RNA hairpin has been generated through in vitro transcription and treated with Pt-ACRAMTU. Our goal was to determine if specific RNA structural motifs are susceptible to intercalator-driven platination. Acidic digestion assays in conjunction with liquid chromatography-electrospray mass spectrometry analysis (LC-ESMS) was used to determine the specific bases modified by platinum. In addition, the RNA conformational changes induced by ACRAMTU and PT-ACRAMTU were also analyzed by circular dichroism (CD) spectroscopy.","abstract_has_math":false,"creators":["Vasquez-Valdivieso, Montserrat Guadalupe"],"institution":"Wake Forest University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2009,"date_issued":"2009-08-18T15:15:36Z","date_published":"2009-08-18T15:15:36Z","updated_at":"2026-07-27T22:01:01Z","subjects":["Biochemistry"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10339/14770","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Vasquez-Valdivieso, Montserrat Guadalupe"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2009-08-18T15:15:36Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2009-08-18T15:15:36Z"]},{"key":"dc:date.issued","label":"Date","values":["2009-08-18T15:15:36Z"]},{"key":"dc:publisher","label":"Institution","values":["Wake Forest University"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biochemistry"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/10339/14770"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Pt-ACRAMTU (ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea) is a DNA-targeted anticancer agent that shows activity in a broad range of solid tumor cell lines. Unlike the classical platinum-based cross-linking drugs, this agent produces its cytotoxic effect by two synergistic DNA binding mechanisms: monofunctional platination and intercalation of the acridine chromophore. The RNA binding of platinum drugs has been studied to a much lesser extent. Recently, the RNA interactions of platinum-containing drugs and drug conjugates have been reported. In the current study, an RNA hairpin has been generated through in vitro transcription and treated with Pt-ACRAMTU. Our goal was to determine if specific RNA structural motifs are susceptible to intercalator-driven platination. Acidic digestion assays in conjunction with liquid chromatography-electrospray mass spectrometry analysis (LC-ESMS) was used to determine the specific bases modified by platinum. In addition, the RNA conformational changes induced by ACRAMTU and PT-ACRAMTU were also analyzed by circular dichroism (CD) spectroscopy."]},{"key":"dc:title","label":"Title","values":["CHARACTERIZATION OF THE RNA BINDING MODE OF A PLATINUM-ACRIDINE AGENT"]}]}],"canonical_facts":{"dc:creator":["Vasquez-Valdivieso, Montserrat Guadalupe"],"dc:date.accessioned":["2009-08-18T15:15:36Z"],"dc:date.available":["2009-08-18T15:15:36Z"],"dc:date.issued":["2009-08-18T15:15:36Z"],"dc:description.abstract":["Pt-ACRAMTU (ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea) is a DNA-targeted anticancer agent that shows activity in a broad range of solid tumor cell lines. Unlike the classical platinum-based cross-linking drugs, this agent produces its cytotoxic effect by two synergistic DNA binding mechanisms: monofunctional platination and intercalation of the acridine chromophore. The RNA binding of platinum drugs has been studied to a much lesser extent. Recently, the RNA interactions of platinum-containing drugs and drug conjugates have been reported. In the current study, an RNA hairpin has been generated through in vitro transcription and treated with Pt-ACRAMTU. Our goal was to determine if specific RNA structural motifs are susceptible to intercalator-driven platination. Acidic digestion assays in conjunction with liquid chromatography-electrospray mass spectrometry analysis (LC-ESMS) was used to determine the specific bases modified by platinum. In addition, the RNA conformational changes induced by ACRAMTU and PT-ACRAMTU were also analyzed by circular dichroism (CD) spectroscopy."],"dc:identifier.uri":["http://hdl.handle.net/10339/14770"],"dc:language.iso":["en"],"dc:publisher":["Wake Forest University"],"dc:subject":["Biochemistry"],"dc:title":["CHARACTERIZATION OF THE RNA BINDING MODE OF A PLATINUM-ACRIDINE AGENT"],"dc:type":["Thesis"]},"updated_at":"2026-07-27T22:01:01Z"}