Synthesis of Unmodified Oligonucleotides
Synthesis of Unmodified Oligonucleotides
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未修饰寡核苷酸的合成
DOI：
10.1002/0471142700.nc0300s45
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发表时间：
2011
影响因子：
--
通讯作者：
P. Herdewijn
中科院分区：
文献类型：
--
作者：
S. Beaucage;P. Herdewijn
B由于在过去40年中在化学合成寡核苷酸方面取得了重大进展，人工合成的寡核苷酸已经变得容易获得，并推动了生物技术革命，这场革命不可逆转地改变了生物医学研究和制药业。例如，如果没有快速有效地合成DNA寡核苷酸的能力，聚合酶链式反应(PCR)及其多种应用的发展将是困难的，如果不是不可能的，因为这项技术完全依赖于DNA引物的使用。同样，合成寡核苷酸的可获得性也有助于DNA自动测序的发展，这也依赖于DNA引物的使用。人工合成寡核苷酸的一个重要生物学应用与基因的定点突变有关。这种类型的突变已被用于研究蛋白质结构-功能关系和改变具有药物活性的蛋白质的治疗光谱。人工合成的寡核苷酸还被用作诊断杂交探针，最近还被用于高通量检测遗传病和鉴定基因组单核苷酸多态的DNA芯片。此外，合成的RNA寡核苷酸的可获得性导致了核酶的制备，核酶是具有催化活性的RNA。在这方面，人们推测RNA可能是生命起源的主要自我复制分子。总而言之，合成DNA和RNA寡核苷酸的多种生物医学应用是快速有效地制备这些生物分子的方法对生命科学产生的巨大影响的直接衡量。
B ecause of the significant progress achieved in the chemical synthesis of oligonucleotides during the past four decades, synthetic oligonucleotides have become readily available and have fueled the biotechnology revolution that has irreversibly changed biomedical research and the pharmaceutical industry. For example, without the ability to rapidly and efficiently synthesize DNA oligonucleotides, the development of the polymerase chain reaction (PCR) and its multiple applications would have been difficult, if not impossible, because this technology is completely dependent upon the use of DNA primers. Similarly, the availability of synthetic oligonucleotides has been instrumental in the development of automated DNA sequencing, which is also dependent on the use of DNA primers. An important biological application of synthetic oligonucleotides relates to site-specific mutagenesis of genes. Mutagenesis of this type has been utilized to study protein structure-function relationships and to alter the therapeutic spectrum of pharmaceutically active proteins. Synthetic oligonucleotides have also found application as diagnostic hybridization probes and, more recently, in the use of DNA chips for highthroughput detection of genetic diseases and identification of genomic single-nucleotide polymorphisms. Furthermore, the availability of synthetic RNA oligonucleotides has led to the preparation of ribozymes, which are RNAs with catalytic activity. In this regard, it is being speculated that RNA may have been the primary self-replicating molecule from which life originated. Collectively, the multiple biomedical applications of synthetic DNA and RNA oligonucleotides are a direct measure of the colossal impact the methods for rapid and efficient preparation of these biomolecules have had on the life sciences.