Peptide-Peptide Nucleic Acid Conjugates for Modulation of Gene Expression
Peptide-Peptide Nucleic Acid Conjugates for Modulation of Gene Expression
复制标题
DOI：
10.1039/9781847558275-00080
复制
发表时间：
2008-01-01
期刊：
影响因子：
--
通讯作者：
Gait, Michael J.
中科院分区：
文献类型：
--
作者：
Fabani, Martin M.;Ivanova, Gabriela D.;Gait, Michael J.
当Zamecnik和Stephenson首次提出合成寡脱氧核糖核苷酸作为结合劳斯肉瘤病毒RNA抑制病毒复制的试剂时，他们设计了一种寡核苷酸（ON）来靶向蛋白质翻译的起始位点，期望它能形成RNA - dna双工并物理阻断RNA，从而阻止蛋白质的合成。几年后，人们发现，当DNA低聚物与细胞内的RNA靶标结合时，可能有另一种机制起作用，即细胞酶RNase H识别杂合体并随后进行RNA切割。DNA离子的第二个属性，延伸到它们的硫代酸修饰的对应物，被确立为主要的“反义”作用机制，并导致了这类治疗性离子的第一次工业发展。抑制蛋白质翻译的位阻机制的最初概念继续被科学家们研究，但直到最近才被认真考虑作为潜在的治疗药物。另外，我们现在知道通过双工
When Zamecnik and Stephenson first proposed synthetic oligodeoxyribonucleotides as reagents to bind to Rous sarcoma virus RNA to inhibit viral replication, they designed an oligonucleotide (ON) to target the initiation site for protein translation in the expectation that it would form an RNA–DNA duplex and physically block the RNA, thus preventing protein synthesis. 1 Several years later it was found that an alternative mechanism probably operates when DNA oligomers bind to RNA targets inside cells, that of recognition of the hybrid by the cellular enzyme RNase H and subsequent RNA cleavage. This second attribute of DNA ONs, which extends to their phosphorothioate-(PS-) modified counterparts, became established as the predominant ‘antisense’mechanism of action and led to the first industrial development of this class of therapeutic ONs. The original concept of the steric block mechanism of inhibition of protein translation continued to be studied by scientists, 2, 3 but only recently have steric block ONs been considered seriously as potential therapeutics. In addition, we now know that through duplex