Novel Synthetic Platforms for the Modifications of Nucleosides

Cuny City College, New York NY

Investigators

Abstract

With the support of the Chemical Synthesis (SYN) program in the Division of Chemistry, Professor Mahesh Lakshman of The City College of New York (CUNY) is studying the development of novel chemical methods for the modifications of nucleosides. Nucleosides are the fundamental building blocks of genetic material, i.e., DNA and RNA. Because of their ubiquity in nature, nucleosides have either been scaffolds or inspiration for the development of novel molecules with diverse applications and utilities. These applications include medicinally and pharmacologically important entities, modification of the genetic code, and as detection tools and probes of biochemical and biological processes. Nucleosides are composed of two parts, a base and sugar. Because of their structural components and multiple reaction sites, the chemical reactivities of nucleosides can be quite complex. The overarching goal of this work will be to obtain a fundamental understanding of chemical processes to achieve desired selective modifications of the nucleoside family of compounds. Professor Lakshman’s research group consists of undergraduate and graduate students, as well as postdoctoral associates. Thus, trainees at all educational levels will cohesively contribute to the research goals. Students obtain professional hands-on experience in planning, developing, and performing chemical reactions, as well as the purification and characterization of products. They also learn a variety of soft skills such as teamwork, and both oral and written dissemination of scientific information. A focus will be placed on providing professional preparation for trainees, enabling them to succeed in the next stages of their careers. Nucleosides are ubiquitous biomolecules, present in all living systems and in viruses. The importance of modified nucleosides is broadly encompassing. Nucleosides have been central to the development of pharmacologically and therapeutically important entities, oligonucleotide therapeutics, aptamer discovery, studies on xeno nucleic acids, extension of the genetic alphabet, studies on unusual base pairing, and probes for biological and biochemical processes. Nucleosides contain a polynitrogenated base attached to a saccharide, and their reactivities can be quite complex. Understanding reactions of bifunctionalizable nucleoside derivatives, C–H bond activation reactions, radical reactions, and development of novel fluorescent nucleosides, will provide access to innovative molecular paradigms for new applications. Participation of undergraduate and graduate students, as well as postdoctoral associates, in the research endeavor prepares them for their professional careers. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.