分子重构技术_【介绍】重构DNA双链分子的PNA技术

不知道大家听说过Peptide nucleic acid (PNA)技术没有？！我以前就自个想有没有通过化学的方面使得DNA分子“刚性化”，从而带来一场革命，想不到偶然间发现真的有这种技术，个人认为这种技术未来会大行其便，

Synthetic molecules that can bind with high sequence specificity to a chosen target in a gene sequence are of major interest in medicinal and biotechnological contexts. They show promise for the development of gene therapeutic agents, diagnostic devices for genetic analysis, and as molecular 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 Peptide nucleic acid (PNA) is a nucleic acid analog in which the sugar phosphate backbone of natural nucleic acid has been replaced by a synthetic peptide backbone usually formed from N-(2-amino-ethyl)-glycine units, resulting in an achiral and uncharged mimic(拟态，模拟物). It is chemically stable and resistant to hydrolytic (enzymatic) cleavage and thus not expected to be degraded inside a living cell. PNA is capable of sequence-specific recognition of DNA and RNA obeying the Watson-Crick hydrogen bonding scheme, and the hybrid complexes exhibit extraordinary thermal stability and unique ionic strength effects. It may also recognize duplex homopurine sequences of DNA to which it binds by strand invasion, forming a stable PNA-DNA–PNA triplex(三体复合物) with a looped-out DNA strand. Since its discovery, PNA has attracted major attention at the interface of chemistry and biology because of its interesting chemical, physical, and biological properties and its potential to act as an active component for diagnostic as well as pharmaceutical(药物，药学的) applications. In vitro studies indicate that PNA could inhibit both transcription and translation of genes to which it has been targeted, which holds promise for its use for antigene and antisense therapy. However, as with other high molecular mass drugs, the delivery of PNA, involving passage through the cell membrane, appears to be a general problem.—Ray, A., Nordén, B. Peptide nucleic acid (PNA): its medical and biotechnical applications and promise for the future.

什么是？PNAs are DNA analogs(类似物) in which a 2-aminoethyl-glycine linkage generally replaces the normal phosphodiester backbone. A methyl carbonyl linker connects natural as well as unusual (in some cases) nucleotide bases to this backbone at the amino nitrogens. This simple and yet entirely new synthetic molecule has an interesting and nonprototype chemistry. PNAs are non-ionic, achiral molecules and are not susceptible to hydrolytic (enzymatic) cleavage. Despite all these variations from natural nucleic acids, PNA is still capable of sequence-specific binding to DNA as well as RNA obeying the Watson-Crick hydrogen bonding rules. Its hybrid complexes exhibit extraordinary thermal stability and display unique ionic strength properties.

用途：today there are three to four major groups of applications for this novel compound. First, it can be used as a molecular tool in molecular biology and biotechnology . Second is its role as lead compound for the development of gene-targeted drugs applying antigene or antisense strategy. Third is the use of PNA for diagnostics purposes and development of biosensors. Fourth, the study of basic chemistry is related to PNA for the improvement of basic architecture, e.g., for supramolecular constructs and to possibly generate a subsequent generation of PNA molecules.

详见：http://www.fasebj.org/cgi/content/full/14/9/1041

http://nar.oupjournals.org/cgi/content/full/24/3/494

我之所以发现这个是因为一直在关注RNAi技术在原核生物的进展，结果发现RNAi技术在原核生物中难以实现，而这种技术在原核生物里面有替代RNAi技术的可能。