Abstract:
The thesis entitled “Supramolecular assemblies of C-bimodal PNAs to tetraplexes and triple duplexes and biophysical studies of C5 substituted Uracil PNA Oligomers” comprises of a systematic study of formation of i-Motif structures and silver mediated higher order assemblies from bimodal peptide nucleic acid (bm-PNA) and the impact of C5-Uracil modification on PNA:DNA/RNA/PNA hybrids.The bimodal PNAs (bm-PNA) are a new class of PNA molecules which can bind two different cDNAs to form double duplexes. The bimodal PNA oligomers having all-Cytosines (C) on C side chains are shown to have potential to form i-Motif structure (C:H+:C) at acidic pH. Such i-Motifs from triazole face of bm-PNA possess nucleobases on amide face to which can bind to a complementary DNA strand with potential to form duplexes from outer side. bm-PNA having all-C can also self-pair through mediation of metal ions at neutral pH. This leads to a bm-PNA:Ag+:bm-PNA duplex, which can in turn form outer duplexes with DNA leading to formation of triple duplexes. Such metal mediated base pairing (C:M+:C) of bm-PNA presents a promising strategy to generate self-assembling supramolecules with metal-based functionality. The work also describes effects of hydrophilic, hydrophobic, lipophilic C5-U modifications on PNA:DNA/RNA/PNA hybrids.
