Orthogonal Crosslinking: A Strategy to Generate Novel Protein Topology and Function.
Orthogonal Crosslinking: A Strategy to Generate Novel Protein Topology and Function.
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正交交联：生成新型蛋白质拓扑和功能的策略。
DOI：
10.1002/chem.202202828
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Lin,Qing
中科院分区：
文献类型：
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作者：
Wang,Zheng;Rabb,JohnathanD;Lin,Qing
与二硫键相比，其他天然存在的分子内交联很少受到关注，可能是因为它们在广阔的蛋白质空间中很少见。在这里，我们提出了天然非二硫键交联的例子，我们称之为正交交联，强调它们对蛋白质拓扑结构和功能的影响。我们总结了最近的努力扩大正交交联使用酶催化蛋白质环化或遗传密码扩展策略，以增加亲电氨基酸位点特异性的蛋白质。每种方法的优点和缺点进行了讨论，沿着与他们的应用，以产生新的蛋白质拓扑结构和功能。特别是，我们强调了我们最近的工作自发正交交联，其中氨基甲酸酯基交联原位生成，及其在设计正交交联结构域抗体与它们的拓扑模拟细菌粘附素的应用。
Compared to the disulfide bond, other naturally occurring intramolecular crosslinks have received little attention, presumably due to their rarity in the vast protein space. Here we presented examples of natural non‐disulfide crosslinks, which we refer to as orthogonal crosslinks, emphasizing their effect on protein topology and function. We summarize recent efforts on expanding orthogonal crosslinks by using either the enzymes that catalyze protein circularization or the genetic code expansion strategy to add electrophilic amino acids site‐specifically in proteins. The advantages and disadvantages of each method are discussed, along with their applications to generate novel protein topology and function. In particular, we highlight our recent work on spontaneous orthogonal crosslinking, in which a carbamate‐based crosslink was generated in situ, and its applications in designing orthogonally crosslinked domain antibodies with their topology‐mimicking bacterial adhesins.