Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, 1600 Huron Parkway, NCRC B520, Ann Arbor, Michigan 48109, USA.
Chem Commun (Camb). 2018 Jun 19;54(50):6531-6539. doi: 10.1039/c8cc02332h.
Click chemistry has emerged as a powerful tool in our arsenal for unlocking new biology. This includes its utility in both chemical biology and drug discovery. An emerging application of click chemistry is in the development of biochemical assays for high-throughput screening to identify new chemical probes and drug leads. This Feature Article will discuss the advancements in click chemistry that were necessary for the development of a new class of biochemical assay, catalytic enzyme-linked click chemistry assay or cat-ELCCA. Inspired by enzyme immunoassays, cat-ELCCA was designed as a click chemistry-based amplification assay where bioorthogonally-tagged analytes and enzymes are used in place of the enzyme-linked secondary antibodies used in immunoassays. The result is a robust assay format with demonstrated applicability in several important areas of biology and drug discovery, including post-translational modifications, pre-microRNA maturation, and protein-protein and RNA-protein interactions. Through the use of cat-ELCCA and other related click chemistry-based assays, new chemical probes for interrogating promising drug targets have been discovered. These examples will be discussed, in addition to a future outlook on the impact of this approach in probe and drug discovery.
点击化学已成为我们解锁新生物学的有力工具。这包括其在化学生物学和药物发现中的应用。点击化学的一个新兴应用是开发用于高通量筛选的生化分析，以鉴定新的化学探针和药物先导物。这篇专题文章将讨论点击化学的进展，这些进展对于开发一种新的生化分析方法，即催化酶联点击化学分析或 cat-ELCCA 是必要的。受酶免疫分析的启发，cat-ELCCA 被设计为一种基于点击化学的扩增分析方法，其中生物正交标记的分析物和酶代替了免疫分析中使用的酶联二级抗体。结果是一种强大的分析方法，在包括翻译后修饰、前 microRNA 成熟、蛋白质-蛋白质和 RNA-蛋白质相互作用在内的几个重要生物学和药物发现领域都具有适用性。通过使用 cat-ELCCA 和其他相关的点击化学分析方法，已经发现了用于研究有前途的药物靶点的新化学探针。除了讨论这种方法在探针和药物发现中的未来前景外，还将讨论这些例子。
