Peptide nucleic acid targeting of double-stranded DNA

Abstract

Publisher Summary The DNA mimic PNA (peptide nucleic acid) was originally conceived and designed as a DNA major groove-binding ligand mimicking triple helix-forming oligonucleotides. In a chemical sense PNA oligomers are much more closely related to peptides and proteins than they are to oligonucleotides. Structurally, however, PNA oligomers are good mimics of DNA or RNA and they form tight helical duplexes with sequence complementary DNA, RNA (or PNA) oligomers. This chapter describes four different binding modes on targeting double-stranded DNA with PNAs. These include conventional triplex binding in the major groove of the DNA double helix and triplex invasion in which two preferably antiparallel PNA oligomers invade and open this DNA double helix through formation of an internal PNA–DNA–PNA Watson–Crick–Hoogsteen triplex. Duplex invasion through an internal PNA-DNA Watson-Crick duplex has also been observed under certain conditions, and if special modified pseudo-complementary bases, such as the diaminopurine–thiouracil base pair, are employed in the PNA oligomers, binding to the target by double duplex invasion is possible. The results obtained so far clearly show that PNA is an interesting and useful reagent for sequence-specific targeting of double-stranded DNA.