cat-ELCCA: catalyzing drug discovery through click chemistry

Abstract

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.