chapter  5
14 Pages

Peptide nucleic acids (PNA) binding-mediated target gene transcription

ByGAN WANG, XIAOXIN XU

INTRODUCTION Peptide nucleic acids (PNAs) are synthetic oligonucleotides with modified backbones (Figure 5.1) (Nielsen et al., 1991). In PNAs, the deoxyribose phosphate backbones are replaced with polyamide backbones. PNAs can bind to DNA and RNA targets in a sequence-specific manner to form PNA/DNA and PNA/RNA Watson-Crick double helical structures. When binding to double-stranded DNA targets, the PNA molecule replaces one DNA strand in the target duplex by strand displacement, while the displaced DNA strand exists as a single-stranded D-loop at the PNA binding site (Kurakin et al., 1998; Lohse et al., 1999; Nielsen et al., 1991). A [PNA]2/DNA triple helix structure can form when PNAs bind to a homopurine/ homopyrimidine sequence (Figure 5.2). In this case, a second molecule of PNA binds to the DNA strand of the PNA/DNA duplex by Hoogsteen hydrogen bonds to form a triplex structure at the target site and the displaced DNA strand remains as a single stranded D-loop (Hanvey et al., 1992; Nielsen et al., 1991). Studies have shown that the triplexes formed with PNAs are pyrimidine-motif in that the pyrimidine PNA strand binds parallel to the purine strand in DNA targets

Figure 5.1 Structures of DNA and PNA oligonucleotides.