Session 1C: Inaugural Lectures by Fellows / Associates

Nucleic acids directed synthesis for therapeutic applications

Abstract: Nucleic acids play crucial roles in transfer of cellular information as well as gene regulations. DNA and RNA have been implicated in many human diseases, thereby offering opportunities for exploring small molecule-based therapeutics. However, development of target-selective molecules possessing well-defined biological activity has always been challenging. In the current scenario of continuous threat of infectious disease outbreaks, it is important to expand the scope of chemical toolsets to assist conventional drug discovery strategies for the easy identification and optimization of therapeutically relevant drug candidates. Template directed synthesis (TDS) is a promising tool for rapid drug discovery as it allows a biological target to template the selection or synthesis of its own ligands from a pool of reactive fragments. There are two main strategies of TDS: dynamic combinatorial chemistry (DCC) and kinetically controlled target-guided in situ synthesis. Though discovered only two decades ago, as compared to protein targets, nucleic acid templated TDS techniques are relatively unexplored in the arena of drug discovery. In this talk, I would like discuss the use of TDS approaches for the synthesis of selective ligands for nucleic acid targets like DNA quadruplexes, i-motifs and HIV-TAR RNA.