2026-09-20T09:46:06Zhttps://wakespace.lib.wfu.edu/server/oai/request

oai:null:10339/364162026-09-18T12:36:41Zcom_10339_14934col_10339_38132

Dutta, Samrat 2012-01-18T09:35:22Z 2014-01-18T09:30:11Z 2011 https://wakespace.lib.wfu.edu/handle/10339/36416 In my dissertation research I have used atomic force microscopy (AFM), simulations and molecular biology to investigate different classes of therapeutics. Many cancer drugs bind to DNA and inhibit replication. We have AFM and simulations, based on the worm-like chain model (WLC), to study DNA conformational changes due to its interaction with two cancer drugs, cisplatin and Pt-Acramtu. We found that cisplatin induces a 36º bend angle for a cisplatin-GG adduct and 0 - 19º for a cisplatin-AG adduct. Overall DNA flexibility did not change due to these interactions with a single cisplatin molecule, but DNA softens around the damage site. The intercalating drug Pt-Acramtu lengthens DNA by 0.45 - 0.6 nm/drug molecule, but does not change DNA flexibility, for 2-30 % drug to base pair ratio. The higher doses of Pt-Acramtu induced DNA loops and aggregation, and the highest doses caused DNA double-strand breaks. en Wake Forest University STUDYING THE INTERACTION OF CANCER AND THROMBOSIS THERAPEUTICS WITH PROTEIN AND DNA Dissertation Guthold, Martin Vaughn, James P Kim-Shapiro, Daniel B Macosko, Jed C Salsbury Jr, Freddie R Physics 2014-01-18 restricted