Discovery of new inhibitor for the protein arginine deiminase type 4 (PAD4) by rational design of α-enolase-derived peptides

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease affecting about 0.24 % of the world population. Protein arginine deiminase type 4 (PAD4) believed to be responsible for occurrence RA by catalyzing citrullination proteins. The citrullinated proteins act as autoantigens stimulating immune response. Citrullinated α-enolase has been identified one RA. Hence, serves a suitable template design potential peptide inhibitors against PAD4. binding affinity α-enolase-derived peptides and PAD4 was virtually determined using PatchDock HADDOCK docking programs. Synthesis designed performed solid phase synthesis method. inhibitory each experimentally inhibition assay IC50 measurement. data show that N-P2 most favourable substrate among all peptides. Further modification changing Arg residue canavanine [P2 (Cav)] rendered it inhibitor reducing activity 35 with 1.39 mM. We conclude P2 (Cav) can serve starting point development even more potent inhibitors.