A Naturally Encoded Dipeptide Handle for Bioorthogonal Chan-Lam Coupling
A Naturally Encoded Dipeptide Handle for Bioorthogonal Chan-Lam Coupling
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DOI：
10.1002/anie.201800828
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发表时间：
2018-04-03
影响因子：
16.6
通讯作者：
Ball, Zachary T.
中科院分区：
文献类型：
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作者：
Ohata, Jun;Zeng, Yimeng;Ball, Zachary T.
生物大分子的操纵理想地通过遗传编码的、天然存在的官能团的独特的和生物正交的化学反应来实现。用于位点特异性缀合的方法的工具箱受到选择性问题和缺乏具有正交反应性的天然存在的官能团的限制。我们报告，焦谷氨酸酰胺N-H键表现出生物正交铜催化的Chan-Lam偶联在焦谷氨酸-组氨酸二肽序列。焦谷氨酸残基很容易通过天然酶促途径掺入感兴趣的蛋白质中，从而允许在最低限度的二肽标签处进行特异性生物缀合。
Manipulation of biomacromolecules is ideally achieved through unique and bioorthogonal chemical reactions of genetically encoded, naturally occurring functional groups. The toolkit of methods for site-specific conjugation is limited by selectivity concerns and a dearth of naturally occurring functional groups with orthogonal reactivity. We report that pyroglutamate amide N-H bonds exhibit bioorthogonal copper-catalyzed Chan-Lam coupling at pyroglutamate-histidine dipeptide sequences. The pyroglutamate residue is readily incorporated into proteins of interest by natural enzymatic pathways, allowing specific bioconjugation at a minimalist dipeptide tag.