Nucleic Acid Backbone Structure Variations: Peptide Nucleic Acids

Abstract

Abstract Synthetic analogues and mimics of the natural genetic material deoxyribonucleic acid (DNA) are potential gene therapeutic (antisense or antigene) drugs. One of these mimics, peptide nucleic acids (PNAs), are chemically closer to peptides and proteins than to DNA, but nonetheless have retained many of the structural properties of DNA. These molecules have found applications as probes in genetic diagnostics and are also being developed into antisense (ribonucleic acid (RNA) interference) gene therapeutic drugs, targeting selected genes through sequence‐specific recognition of (messenger or micro)RNA, and in the future also antigene applications targeting the double‐stranded DNA of the genes themselves leading to gene silencing or guiding specific gene repair. Finally, the special chemical and structural properties of PNA suggest that these or similar molecules might have played a role in the prebiotic origin of life (on Earth) and also could be interesting components of possible artificial life. Key Concepts: Peptide nucleic acid (PNA) is a DNA mimic in which the backbone consists of a charge neutral pseudo peptide. Peptide nucleic acids can be designed to bind sequence selectively to duplex DNA and thus may function as ‘antigene’ drugs. A range of chemical structures can mimic various functions of our genetic material, the DNA. Chemical modifications and structural mimics of DNA are useful as genetic diagnostic probes and are being developed into gene therapeutic drugs. RNA interference drug sequences specifically bind to cellular (messenger or micro)‐RNA and interfere with (inhibit) their function. Prebiotic origin of life could have involved peptide nucleic acid molecules as predecessors of RNA.