Development of thiazole orange-carrying peptide nucleic acid small molecule conjugate probes for the promoter region of Influenza A virus
概要
This thesis comprises of five chapters:
Chapter 1: Since the emergence of drug resistant Influenza A Virus (IAV) strains due to genetic mutation, new
classes of drug candidate targeting the IAV became highly desirable. In this chapter, we exploit the knowledge
of the IAV RNA promoter region, which is a conserved region in the virus that is not involved in the genetic
variations associated with pathogenesis and antiviral resistance. We propose a new strategy of conjugating DPQ
small molecule that has antiviral potentials and targets the internal loop of this region, with a triplex forming
PNA oligomer that recognizes the double stranded structure. In this probe design, thiazole orange fluorophore
that is internally incorporated into the probe is adopted. This resulting conjugate (tFIT-DPQ) showed a
significant light-up response (83-fold) upon strong (Kd =185 nM) and selective binding to the target RNA under
physiological conditions (pH 7.0, 100 mM NaCl), overcoming pH limitation. All relevant experiments
explaining this novel concept were discussed fully in this chapter. ...