Protein conjugation with genetically encoded unnatural amino acids.

Protein conjugation with genetically encoded unnatural amino acids.
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DOI:
10.1016/j.cbpa.2013.04.017
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发表时间:
2013-06
影响因子:
7.8
通讯作者:
Schultz, Peter G.
Schultz, Peter G.
中科院分区:
生物学2区
文献类型:
--
作者:
Kim, Chan Hyuk;Axup, Jun Y.;Schultz, Peter G.

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具有正交化学反应性的非天然氨基酸位点特异性掺入蛋白质中使得能够合成结构确定的蛋白质缀合物。含有酮、叠氮化物、炔、烯烃和四嗪侧链的氨基酸可以响应于无义和移码密码子而被遗传编码。这些生物正交化学手柄允许对缀合的位点和化学计量进行精确控制,并且使得能够对蛋白质缀合物的物理和生物学性质进行药物化学样优化,特别是下一代蛋白质治疗剂。
The site-specific incorporation of unnatural amino acids with orthogonal chemical reactivity into proteins enables the synthesis of structurally-defined protein conjugates. Amino acids containing ketone, azide, alkyne, alkene, and tetrazine side chains can be genetically encoded in response to nonsense and frameshift codons. These bio-orthogonal chemical handles allow precise control over the site and stoichiometry of conjugation, and have enabled medicinal chemistry-like optimization of the physical and biological properties of protein conjugates, especially the next-generation protein therapeutics.
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