Peptide Nucleic Acid (PNA)-GalNAc Conjugates for Targeted Cellular Delivery and C-gama(S/R)-Janus PNAs for Double Duplex Formation with cDNA

Abstract

The thesis is comprised of two components. The first part deals with studies on peptide nucleic acids (PNA) which are conjugated to triantennary N- acetyl galactosamine (GalNAc) for targeted delivery to hepatocytes via asialoglycoprotein receptor (ASGPR)1. This receptor is abundantly expressed exclusively on hepatocytes and clears glycoproteins and desialylated platelets2. Inspired from recent reports of siRNAs conjugated with GalNAc efficiently permeating hepatocyte cells, the work presented in this thesis aims to conjugate triantennary GalNAc to PNA and study their entry into hepatocyte derived cells. The second part of thesis is concerned with the design, synthesis and evaluation of an entirely new class of PNA analogues -“Janus PNA” in which a single strand of PNA is designed to carry two sets of nucleobase sequences, one set same as the standard t-amide linked bases as in standard PNA and the other set linked at C on backbone through a secondary amide linker. Such Janus PNAs can simultaneously bind to two cDNA sequences and opens up a new paradigm for PNA recognition by cDNA for biological and material applications.