Phosphorothioate oligonucleotides: chemistry, purification, analysis, scale-up and future directions.
Phosphorothioate oligonucleotides: chemistry, purification, analysis, scale-up and future directions.
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硫代磷酸酯寡核苷酸：化学、纯化、分析、放大和未来方向。
DOI：
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发表时间：
1991
期刊：
影响因子：
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通讯作者：
T. Geiser
中科院分区：
文献类型：
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作者：
G. Zon;T. Geiser
硫代修饰的寡核苷酸作为序列特异性试剂在体外和体内作为药物来控制转录、剪接、翻译和其他调控过程，受到了广泛和日益增长的兴趣。这些令人兴奋的应用是基于硫代寡核苷酸对核酸酶降解的抵抗力，这一特性只是由于将硫结合到磷酸骨架中而产生的。硫代寡核苷酸类似物的流行源于它们的几个特点：相对容易的自动化合成，简单的提纯和处理，以及在水中的高溶解度。本文介绍了目前的制备和分析方法，以及用于临床评估的制备硫代寡核苷酸作为原料药的固相和溶液工艺的综合比较分析。对未来提出了前瞻性的展望，希望将注意力集中在需要研究的重要领域，特别是涉及硫代寡核苷酸技术的研究，以及一般核酸药物的制造。
There is widespread and growing interest in the use of phosphorothioate-modified oligonucleotides as sequence-specific agents to control transcription, splicing, translation and other regulated processes in vitro and in vivo, as pharmaceuticals. These exciting applications are predicated on the resistance of phosphorothioate oligonucleotides to degradation by nucleases, a property that results simply from incorporation of sulfur into the phosphate backbone. The popularity of phosphorothioate oligonucleotide analogs derives from several of their features: relatively easy automated synthesis, uncomplicated purification and handling, plus high solubility in water. Presented here are current preparative and analytical methods, together with a comprehensive comparative analysis of solid-phase and solution processes for manufacturing phosphorothioate oligonucleotides as bulk pharmaceutical compounds for clinical evaluation. A prospective view of the future is offered with the hope of directing attention to important areas of needed research dealing with phosphorothioate oligonucleotide technology in particular, and manufacturing of nucleic acid pharmaceuticals in general.