Chemically Modified Oligonucleotides as Probes and Inhibitors
Chemically Modified Oligonucleotides as Probes and Inhibitors
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作为探针和抑制剂的化学修饰寡核苷酸
DOI：
10.1002/anie.199106133
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发表时间：
1991
影响因子：
--
通讯作者：
Gauss Dh
中科院分区：
文献类型：
--
作者：
U. Englisch;Gauss Dh
如果存在互补的反平行核苷酸序列，则寡核苷酸特异性结合至单链核酸以形成双螺旋。此外，某些寡核苷酸特异性结合多种蛋白质。因此，涉及这些核酸或蛋白质的生物过程可以通过添加相应的寡核苷酸来调节（通常被抑制）。这些寡核苷酸的作用和潜在的应用领域可以通过引入化学修饰的核苷酸来拓宽。例如，用甲基膦酸酯取代寡核苷酸磷酸基团导致每个核苷酸失去一个负电荷，并且寡核苷酸变得更亲脂。携带反应基团的寡核苷酸可以修饰其结合配偶体。与染料共价连接的寡核苷酸可以定位在生物样本中。可以检测到非常少量的附着于酶的寡核苷酸，因为酶可以催化大量测定物质的形成（例如，荧光产品）。一个重要的生物化学应用是信使RNA或其基因的检测和定位。医学应用包括细菌或病毒序列的检测。人们对抑制信使RNA的翻译和DNA的转录和复制也很感兴趣。所谓的反义寡核苷酸目前被用于抑制蛋白质生物合成和逆转录病毒的逆转录。
Oligonucleotides bind specifically to single-stranded nucleic acids to form a double helix if there is a complementary antiparallel nucleotide sequence. In addition, certain oligonucleotides bind specifically to a variety of proteins. Therefore, biological processes involving these nucleic acids or proteins can be modulated (normally inhibited) by addition of the respective oligonucleotides. The effects of these oligonucleotides and the fields of potential application can be broadened by the introduction of chemically modified nucleotides. For instance, replacing oligonucleotide phosphate groups by methylphosphonates results in the loss of one negative charge per nucleotide and the oligonucleotide becomes more lipophilic. An oligonucleotide carrying a reactive group can modify its binding partner. An oligonucleotide covalently linked to a dye can be localized in a biological specimen. Oligonucleotides attached to an enzyme can be detected in very small amounts since the enzyme can catalyze the formation of large amounts of the substance assayed (e.g., a fluorescent product). An important biochemical application is the detection and localization of a messenger RNA or its gene. Medical applications include the detection of bacterial or viral sequences. There is also great interest in inhibiting the translation of messenger RNA and the transcription and replication of DNA. So-called antisense oligonucleotides are currently being used for the inhibition of protein biosynthesis and of reverse transcription of retroviruses.