Picking the PAD lock: Chemical and biological approaches to identify PAD substrates and inhibitors

Abstract

In this chapter, we first introduce the protein arginine deiminases (PADs) and then highlight several chemical and biological tools and methods that have greatly enhanced our understanding of the role of the human PADs in health and disease. While the detection of citrullinated proteins has classically proven difficult, new chemical probes that expand our detection capabilities past the realm of antibodies are proving pivotal in identifying new PAD substrates. The continued discovery of the role PADs play in multiple inflammatory diseases and cancer makes them viable therapeutic targets and drives the continued structure-based development of potent and specific inhibitors and chemical probes for this enzyme family.