An improved synthesis of haloaceteamidine-based inactivators of protein arginine deiminase 4 (PAD4)

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology



Document Type



Biochemistry | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry | Therapeutics


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, e.g. 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 4 steps at a significantly (12-fold) lower cost.

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Citation: Tetrahedron Lett. 2008 Jul 7;49(28):4383-4385. Link to article on publisher's site


At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.

Related Resources

Link to Article in PubMed