Enzymatic incorporation of LNA nucleotides into DNA strands
Enzymatic incorporation of LNA nucleotides into DNA strands
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DOI：
10.1002/cbic.200600501
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发表时间：
2007-03-26
期刊：
影响因子：
3.2
通讯作者：
Wengel, Jesper
中科院分区：
文献类型：
--
作者：
Veedu, Rakesh N.;Vester, Birte;Wengel, Jesper
由天然存在的核酸组成的寡核苷酸由于其差的生物稳定性而不适合于许多治疗和生物技术应用。因此，已经合成了许多核酸类似物用于与靶标验证研究或治疗分子相关的应用。[1，2]锁核酸（LNA）核苷酸单体是具有固定的C30-内/N-型呋喃糖构象的核酸类似物，其模拟A型螺旋RNA的核糖构象（方案1）。[3-5]LNA修饰的DNA/RNA寡核苷酸对互补单链RNA和单链或双链DNA显示出前所未有的杂交亲和力，并且与天然核酸相比改善了错配识别。[3-7]此外，LNA修饰的寡核苷酸具有生物稳定性高、生物毒性低、水溶性好等特点，在体内外反义研究中显示出重要意义。[8、9]
Oligonucleotides composed of naturally occurring nucleic acids are unsuitable for many therapeutic and biotechnological applications because of their poor biostability. Numerous nucleic acid analogues have therefore been synthesized for applications related to target-validation studies or therapeutic molecules.[1, 2] Locked nucleic acid (LNA) nucleotide monomers are nucleic acid analogues with a fixed C3о-endo/N-type furanose conformation that mimics the ribose conformation of A-type helical RNA (Scheme 1).[3–5] LNA-modified DNA/RNA oligonucleotides display unprecedented hybridization affinities towards complementary single-stranded RNA and single-or doublestranded DNA, and improved mismatch discrimination compared to natural nucleic acids.[3–7] Moreover, LNA-modified oligonucleotides are characterized by high biostability, low toxicity in biological systems and good aqueous solubility, and they have shown their significance in antisense studies both in vitro and in vivo.[8, 9]