Synthesis and Use of a Phosphonate Amidine to Generate an Anti-Phosphoarginine-Specific Antibody

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology, Chemical Biology Interface Program

Publication Date


Document Type



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


Protein arginine phosphorylation is a post-translational modification (PTM) that is important for bacterial growth and virulence. Despite its biological relevance, the intrinsic acid lability of phosphoarginine (pArg) has impaired studies of this novel PTM. Herein, we report for the first time the development of phosphonate amidines and sulfonate amidines as isosteres of pArg and then use these mimics as haptens to develop the first high-affinity sequence independent anti-pArg specific antibody. Employing this anti-pArg antibody, we further showed that arginine phosphorylation is induced in Bacillus subtilis during oxidative stress. Overall, we expect this antibody to see widespread use in analyzing the biological significance of arginine phosphorylation. Additionally, the chemistry reported here will facilitate the generation of pArg mimetics as highly potent inhibitors of the enzymes that catalyze arginine phosphorylation/dephosphorylation.


N-phosphorylation, antibodies, haptens, phosphoarginine, phosphonate amidine

DOI of Published Version



Angew Chem Int Ed Engl. 2015 Oct 12. doi: 10.1002/anie.201506737. [Epub ahead of print] Link to article on publisher's site

Journal/Book/Conference Title

Angewandte Chemie (International ed. in English)

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Link to Article in PubMed

PubMed ID