Anti-Citrulline polyclonal antibody

Developmental changes in the renal expression and activity of argininosuccinate synthase (ASS1) and argininosuccinate lyase (ASL,), enzymes that use citrulline for the production of arginine, have been reported. Thus, the ability of neonates, and especially premature neonates, to produce arginine may be compromised. To determine the utilization of citrulline in vivo. we measured renal expression of ASSI and ASL and conducted citrulline compartmental and noncompartmental kinetics using [N-15]citrulline in pigs of five different ages (from 10 days preterm to 5 wk of age). The tracer was given in substrate amounts to also test the ability of neonatal pigs to use exogenous citrulline. Preterm and term pigs at birth had lower ASSI and ASL expression than older animals, which was reflected in the longer half-life of citrulline in the neonatal groups. The production and utilization of citrulline by 1-wk-old pigs was greater than in pigs of other ages, including 5-wk-old animals. Plasma citrulline concentration was not able to capture these differences in citrulline production and utilization. In conclusion, the developmental changes in renal ASS1 and ASL gene expression are reflected in the ability of the pigs to use citrulline. However, it seems that there is an excess capacity to use citrulline at all ages. including during prematurity, since the bolus dose of tracer did not result in an increase in endogenous citrulline. Our results support the idea that citrulline supplementation in neonatal, including premature, pigs is a viable option to increase arginine availability.

Protein arginine deiminases (PADs) hydrolyze the side chain of arginine to form citrulline. Aberrant PAD activity is associated with rheumatoid arthritis, multiple sclerosis, lupus, and certain cancers. These pathologies established the PADs as therapeutic targets and multiple PAD inhibitors are known. Herein, we describe the first highly potent PAD1-selective inhibitors (1 and 19). Detailed structure-activity relationships indicate that their potency and selectivity is due to the formation of a halogen bond with PAD1. Importantly, these inhibitors inhibit histone H3 citrullination in HEK293TPAD1 cells and mouse zygotes with excellent potency. Based on this scaffold, we also developed a PAD1-selective activity-based probe that shows remarkable cellular efficacy and proteome selectivity. Based on their potency and selectivity we expect that 1 and 19 will be widely used chemical tools to understand PAD1 biology.