Sarah and Chris's paper is accepted for publication in Angewandte Chemie!

Advances in activity-based sensing probes for isoform-selective imaging of enzymatic activity

The cell regulates complicated signaling and metabolism through strict transcriptional, translational, and post-translational regulation. Considerable advances have been achieved for monitoring transcription and translation over the past few decades. Until recently, there have not been generalizable methods for assessing the effects of post-translational regulation on enzymatic activity. Activity-based sensing (ABS) has emerged as a powerful approach for monitoring small-molecule and enzymatic activities within living systems. Initial examples of ABS were applied for measuring general enzymatic activity; however, a recent focus has been on increasing selectivity to selectively monitor a single enzyme or isoform. The highest degree of selectivity is required for differentiating between different enzyme isoforms, where the targets display significant structural similarities as a result of a gene duplications or alternative splicing. This review highlights key examples of isoform-selective probes with a focus on the relevance of isoform differentiation, design strategies to achieve selectivity, and applications in basic biology or in the clinic.