Expansion of the genetic code via expansion of the genetic alphabet.

Expansion of the genetic code via expansion of the genetic alphabet.
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DOI:
10.1016/j.cbpa.2018.08.009
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发表时间:
2018-10
影响因子:
7.8
通讯作者:
Romesberg FE
Romesberg FE
中科院分区:
生物学2区
文献类型:
--
作者:
Dien VT;Morris SE;Karadeema RJ;Romesberg FE

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目前用于扩增遗传密码的方法使得能够将非典型氨基酸(ncAA)位点特异性掺入真核和原核细胞中的蛋白质中。然而,目前的方法受到可能的密码子数量、它们的正交性以及可能它们对蛋白质合成和折叠的影响的限制。另一种方法依赖于非天然碱基对来创建几乎无限数量的真正新密码子,这些密码子可以有效翻译且高度正交,因为它们使用天然对应物所使用的互补氢键以外的力来指导ncAA的掺入。本文综述了在开发功能性非天然碱基对方面取得的进展和成就,并介绍了其用于产生具有扩展遗传字母表的半合成生物体,该扩展遗传密码是其基础。
Current methods to expand the genetic code enable site-specific incorporation of non-canonical amino acids (ncAAs) into proteins in eukaryotic and prokaryotic cells. However, current methods are limited by the number of codons possible, their orthogonality, and possibly their effects on protein synthesis and folding. An alternative approach relies on unnatural base pairs to create a virtually unlimited number of genuinely new codons that are efficiently translated and highly orthogonal because they direct ncAA incorporation using forces other than the complementary hydrogen bonds employed by their natural counterparts. This review outlines progress and achievements made towards developing a functional unnatural base pair and its use to generate semi-synthetic organisms with an expanded genetic alphabet that serves as the basis of an expanded genetic code.
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