The Protein Arginine Deiminases (PADs) hydrolyze arginine residues to form citrulline. This post-translational modification, termed citrullination, is upregulated in several autoimmune disorders including Rheumatoid Arthritis (RA), lupus, and Alzheimer’s disease. While these enzymes are important regulators of gene transcription, the full spectrum of biological activities is relatively underexplored. Herein, I will discuss our development of pan and isozyme specific PAD inhibitors and their use in vitro and in vivo.

I will specifically highlight our efforts to generate next generation panPAD inhibitors as well as PAD2 selective inhibitors for the treatment of sepsis and other inflammatory diseases that are associated with increased levels of PAD2 activity.