Chemical Biology Strategies for Posttranslational Control of Protein Function

A common strategy to understand a biological system is to selectively perturb it and observe its response. Although technologies now exist to manipulate cellular systems at the genetic and transcript level, the direct manipulation of functions at the protein level can offer significant advantages in precision, speed, and reversibility. Combining the specificity of genetic manipulation and the spatiotemporal resolution of light-and small molecule-based approaches now allows exquisite control over biological systems to subtly perturb a system of interest in vitro and in vivo. Conditional perturbation mechanisms may be broadly characterized by change in intracellular localization, intramolecular activation, or degradation of a protein-of-interest. Here we review recent advances in technologies for conditional regulation of protein function and suggest further areas of potential development.