An improved synthesis of haloacetamidine-based inactivators of protein arginine deiminase 4 (PAD4)
CP Causey, PR Thompson - Tetrahedron letters, 2008 - Elsevier
Protein arginine deiminase 4 (PAD4) is an enzyme that hydrolyzes peptidyl arginine
residues to form citrulline and ammonia. This enzyme has been implicated in several
disease states, for example, rheumatoid arthritis, and therefore represents a unique target
for the development of a novel therapeutic. A solution-phase synthesis of Cl-amidine, the
most potent PAD4 inactivator described to date, has been developed. This synthesis
proceeds in 80% yield over four steps at a significantly (12-fold) lower cost.
residues to form citrulline and ammonia. This enzyme has been implicated in several
disease states, for example, rheumatoid arthritis, and therefore represents a unique target
for the development of a novel therapeutic. A solution-phase synthesis of Cl-amidine, the
most potent PAD4 inactivator described to date, has been developed. This synthesis
proceeds in 80% yield over four steps at a significantly (12-fold) lower cost.