Shivalingam Arun, Brown Tom
Department of Chemistry, University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, Oxford, OX1 3TA, U.K.
Biochem Soc Trans. 2016 Jun 15;44(3):709-15. doi: 10.1042/BST20160051.
Naturally occurring DNA is encoded by the four nucleobases adenine, cytosine, guanine and thymine. Yet minor chemical modifications to these bases, such as methylation, can significantly alter DNA function, and more drastic changes, such as replacement with unnatural base pairs, could expand its function. In order to realize the full potential of DNA in therapeutic and synthetic biology applications, our ability to 'write' long modified DNA in a controlled manner must be improved. This review highlights methods currently used for the synthesis of moderately long chemically modified nucleic acids (up to 1000 bp), their limitations and areas for future expansion.
天然存在的DNA由腺嘌呤、胞嘧啶、鸟嘌呤和胸腺嘧啶这四种核碱基编码。然而，对这些碱基进行的微小化学修饰，如甲基化，会显著改变DNA的功能，而更剧烈的变化，如用非天然碱基对替换，则可能扩展其功能。为了在治疗和合成生物学应用中充分发挥DNA的潜力，我们必须提高以可控方式“书写”长链修饰DNA的能力。本综述重点介绍了目前用于合成中等长度化学修饰核酸（长达1000个碱基对）的方法、它们的局限性以及未来扩展的领域。
