Abstract
AbstractIn recent years, there has been considerable interest in developing gene‐targeting drugs. Synthetic molecules that bind effectively with high sequence specificity to a desired target in a particular “destined” gene sequence are of major interest in medicine and molecular biotechnological research. They show hope for the development of gene therapeutic agents, high‐precision diagnostic devices for genetic analysis and convenient tools for nucleic acid manipulations. Peptide nucleic acid (PNA) is a nucleic acid analog in which the sugar–phosphate backbone of natural nucleic acid has been replaced by a synthetic peptide backbone usually formed from N‐(2‐aminoethyl)glycine units resulting in an achiral and uncharged mimic. It is chemically stable and, in contrast to nucleic acids and peptides, is naturally resistant to hydrolytic (enzymatic) cleavage and thereby not expected to be degraded by cell extracts or inside a living cell. It is capable of sequence‐specific recognition of DNA and RNA obeying a Watson–Crick hydrogen bonding scheme and the hybrid complexes exhibit extraordinary thermal stability and unique ionic strength effects. It also recognizes duplex homopurine sequences of DNA to which it binds by strand invasion, forming a stable PNA·DNA–PNA triplex with a looped‐out DNA strand. This potential synthetic mimic of DNA, since its discovery in 1991, has attracted great attention within medicinal chemistry and molecular biology and also various other fields such as organic and physical chemistry because of its interesting chemical and physical properties. It has been regarded to have great potential for both diagnostic and pharmaceutical applications. In vitro studies have shown successful attempts to use PNA as an inhibitor for both transcription and translation of specific genes. This holds promise for using PNA for antigene and antisense therapy. However, the most exciting use of PNA, as an antisense or antigene drug, requires an efficient and safe method to deliver PNA into living cells, a problem that still remains to be solved.
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