Protein conjugation with genetically encoded unnatural amino acids

被引:215
作者
Kim, Chan Hyuk [1 ]
Axup, Jun Y. [2 ,3 ]
Schultz, Peter G. [1 ,2 ,3 ]
机构
[1] Calif Inst Biomed Res, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA
[3] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA
基金
美国国家卫生研究院;
关键词
SITE-SPECIFIC INCORPORATION; TRANSFER-RNA SYNTHETASE; ESCHERICHIA-COLI; BISPECIFIC ANTIBODIES; MAMMALIAN-CELLS; RECOMBINANT PROTEINS; TRANS-CYCLOOCTENES; CLICK CHEMISTRY; CANCER-THERAPY; CODE;
D O I
10.1016/j.cbpa.2013.04.017
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:412 / 419
页数:8
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