Automated linkage of proteins and payloads producing monodisperse conjugates,Chemical Science

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Automated linkage of proteins and payloads producing monodisperse conjugates
Chemical Science ( IF 7.6 ) Pub Date : 2020/01/02 , DOI: 10.1039/c9sc05468e
Igor Dovgan _{1,

2,

3,

4,

5} , Alexandre Hentz _{1,

2,

3,

4,

5} , Oleksandr Koniev _{5,

6,

7} , Anthony Ehkirch _{8,

9,

10,

11,

12} , Steve Hessmann _{8,

9,

10,

11,

12} , Sylvain Ursuegui _{1,

2,

3,

4,

5} , Sébastien Delacroix _{5,

6,

7} , Margaux Riomet _{5,

13,

14,

15} , Frédéric Taran _{5,

13,

14,

15} , Sarah Cianférani _{8,

9,

10,

11,

12} , Sergii Kolodych _{5,

6,

7} , Alain Wagner _{1,

2,

3,

4,

5}

Affiliation

Controlled protein functionalization holds great promise for a wide variety of applications. However, despite intensive research, the stoichiometry of the functionalization reaction remains difficult to control due to the inherent stochasticity of the conjugation process. Classical approaches that exploit peculiar structural features of specific protein substrates, or introduce reactive handles via mutagenesis, are by essence limited in scope or require substantial protein reengineering. We herein present equimolar native chemical tagging (ENACT), which precisely controls the stoichiometry of inherently random conjugation reactions by combining iterative low-conversion chemical modification, process automation, and bioorthogonal trans-tagging. We discuss the broad applicability of this conjugation process to a variety of protein substrates and payloads.

中文翻译：

蛋白质和有效载荷的自动连接产生单分散偶联物

受控的蛋白质功能化在广泛的应用中具有广阔的前景。然而，尽管进行了深入研究，但由于结合过程固有的随机性，官能化反应的化学计量仍然难以控制。利用特定蛋白质底物的特殊结构特征或通过诱变引入反应性手柄的经典方法实质上受到范围的限制或需要大量的蛋白质再造。本文中，我们介绍了等摩尔的天然化学标记（ENACT），该标记通过组合迭代的低转化率化学修饰，过程自动化和生物正交反式来精确控制内在随机共轭反应的化学计量-标记。我们讨论了这种缀合过程对各种蛋白质底物和有效载荷的广泛适用性。

更新日期：2020-02-13

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