Effect of Small Molecules on Nucleic Acid Stability and Improvements to RNA Structure Prediction

Academic Paper from the year 2020 in the subject Biology - Genetics / Gene Technology, grade: 9.0, , course: Cell Biology and Genetics, language: English, abstract: Nucleic acids have proven to be viable targets for small molecule drugs. While many examples of such drugs are detailed in the literature, only a select few have found practical use in a clinical setting. These currently employed nucleic acid targeting therapies suffer from either debilitating off-target side effects or succumb to a resistance mechanism of the target. The need for new small molecules that target nucleic acids is evident. However, designing a novel drug to bind to DNA or RNA requires a detailed understanding of exactly what binding environments each nucleic acid presents. In an effort to broaden this knowledge, the work presented in this thesis details the binding location and affinity of known and novel nucleic acid binding small molecules with targets ranging from simple RNA secondary structure all the way to the complex structure of ribosomal RNA. Specifically, it is shown that the anthracycline classes of antineoplastics prefer to bind at or near mismatch base pairs in both physiologically relevant iron responsive element RNA hairpin constructs as well as DNA hairpin constructs presenting mismatched base pairs. Also characterized in this thesis is a novel class of topoisomerase II / histone deacetylase inhibitor conjugates that display a unique affinity for DNA over RNA. Finally, the novel class of macrolide-peptide conjugates, known as peptolides, is shown to retain potent translation inhibition of the prokaryotic ribosome and identification of a novel binding site for the anthracycline class of drugs and the characterization of the two novel drug designs presented in this thesis will undoubtedly aid in the effort to design and discover new molecules that aim for nucleic acid targets.

Auteur

Kehinde is passionate about helping organisations make sense of and apply academic research to benefit both the firm and the people who work there. He brings over 7 years' experience designing, implementing and evaluating leadership and organisational development interventions across emergency management, research , aged care, education, mental health and not-for-profit sectors. Kehinde is a teacher and researcher at the University of Lagos where He teaches science. His research interests focus on Genetics, Molecular biology, Cell biology, Bio informatics, Cancer research and work environments that promote wellbeing, productivity and thriving. With a background in leadership and talent strategy, his applied industry experience has focused on learning and development, leadership capabilities, research and succession planning. During this time Kehinde had a strong interest in the identification and development of future organizational leaders and her academic work continues in this area