2026-09-20T19:39:12Zhttps://wakespace.lib.wfu.edu/server/oai/request

oai:null:10339/147702026-09-02T12:12:33Zcom_10339_14934col_10339_38132

Vasquez-Valdivieso, Montserrat Guadalupe 2009-08-18T15:15:36Z 2010-06-18T18:58:30Z 2009-08-18T15:15:36Z 2010-06-18T18:58:30Z 2009-08-18T15:15:36Z https://wakespace.lib.wfu.edu/handle/10339/14770 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. en Wake Forest University Biochemistry Medicinal Chemistry CHARACTERIZATION OF THE RNA BINDING MODE OF A PLATINUM-ACRIDINE AGENT Thesis Release the entire work immediately for access worldwide. Alexander, Rebecca Bierbach, Ulrich Dos Santos, Patricia Chemistry open.access