Sakshi Malhotra, “Mechanistic Investigation of Photo-Induced DNA Interstrand Cross-Link (ICL) Formation by Substituted Benzene Analogues”
Mentors: Xiaohua Peng and Nurul Islam Setu, Chemistry & Biochemistry
For cell division, DNA transcription and replication are vital biological processes that require the temporary separation of two strands of duplex DNA. DNA interstrand cross-link (ICL) covalently links two DNA strands preventing them from dissociation which in turn inhibits cell division. Thus, DNA ICL agents are widely used as anticancer agents. In addition, they are also used for DNA damage and repair study, nucleic acid detection and construction of DNA nanomaterials. The objective of this study is to perform a mechanistic investigation of DNA interstrand cross-linking by modified nucleoside upon X-ray or UV irradiation. We have designed several modified nucleosides with modified base moieties as well as bifunctional aromatic rings capable of cross-linking DNA upon photoirradiation. After the synthesis of the modified nucleosides, they will be incorporated into DNA strands by solid-phase DNA synthesis. The photo reactivities of these molecules towards DNA will be investigated by DNA cross-linking assay upon UV- or X-ray irradiation. The mechanism of DNA ICL formation or DNA strand cleavage will be investigated by using different techniques, including radical and carbocation trapping, PAGE analysis of ICL efficiency, NMR and mass analysis of DNA ICL product, etc. The study will help to understand the cross-linking pattern by the modified nucleosides which can assist to optimize the structure of ICL agents with superior biological activity and also focus on ICL damage with its feedback and connection to cancer development and its treatment.
Hello, I really appreciate you for posting my presentation/video. I have been performing Organic chemistry research for almost 1 year now. I started in the year 2020 but unfortunately due to a pandemic, everything was shut down. So, I was out for a little bit. I have been doing research with Dr. Xiaohua Peng’s Laboratory Group. The main project that I am working on is Mechanistic Investigation of Photo-Induced DNA Interstrand Cross-Link (ICL) Formation by Substituted Benzene Analogues which I have talked about in my presentation, and I have performed two types of reactions which are Oxidation of Methyl Group and Reduction of Carboxylic Acid which are also presented above. I will be graduating next semester with a degree in Biomedical Science/ Pre-Med. I work as a Phlebotomist at St. Luke’s medical center for Advocate Aurora. I have loved my time at UWM and in Dr. Peng’s Laboratory and I am really grateful to all my professors and the whole department of Undergraduate Research who supported my research projects.
If you have any questions and/or suggestions, please let me know and I will try my best to answer them.
Thank You
-Sakshi Malhotra
What an impressive grasp this presenter has of complex ideas and compounds. I appreciated the presentation and see a bright future for this student!
Thank you so much.