Peptide-nucleic acids (PNAs): A tool for the development of gene expression modifiers

被引:74
作者
Gambari, R [1 ]
机构
[1] Univ Ferrara, Dept Biochem & Mol Biol, I-44100 Ferrara, Italy
关键词
peptide nucleic acids; triple helix; strand invasion; transcription; antisense; translation; anti-cancer agents; delivey;
D O I
10.2174/1381612013397087
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Peptide nucleic acids (PNAs) represent nucleic acid analogues with unique biochemical properties and of great interest for the development of therapeutic agents. The firstly designed and tested PNAs are molecules in which the sugar-phosphate backbone of DNA was replaced with a pseudopeptide chain constituted by N-(2-aminoethyl) glycine monomers. Nucleobases can be linked to this backbone through a carboxymethyl moiety, which allows to maintain a two atom spacer between the backbone and the bases. Since the first reports on PNAs based on N-(2-aminoethyl) glycine backbone, other PNA analogues have been synthesized, with the main purpose of improve biological activities as well as stability and efficient delivery to target cells. Of great interest are chiral PNAs, PNA analogues bearing phosphate groups (PHONA), PNA-DNA and PNA-peptide chimeras, PNA linked to non-peptide vectors. PNAs hybridize to DNA and RNA with high efficiency following the Watson-Crick hybridization rules, forming highly stable PNA/DNA and PNA/RNA duplexes. In addition, homopyrimidine PNAs, as well as PNAs containing a high pyrimidine:purine ratio, are able to bind to DNA or RNA forming highly stable (PNA)(2)-DNA triple helices. Accordingly, therapeutic PNA and PNA analogues could act as antigene as well as antisense molecules. In addition, recent studies provide evidences for the possible use of PNA-based therapeutic molecules as artificial promoters, as decoy or ribozyme facilitator. Among the therapeutic applications of PNA-based molecules, the most pomising include anti-cancer and anti-viral experimental strategies, but activity of PNAs against bacteria and medically important parasitic organisms have been also reported.
引用
收藏
页码:1839 / 1862
页数:24
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