Synthesis and Use of a Phosphonate Amidine to Generate an Anti-Phosphoarginine-Specific Antibody
UMass Chan Affiliations
Department of Biochemistry and Molecular Pharmacology, Chemical Biology Interface ProgramDocument Type
Journal ArticlePublication Date
2015-10-12Keywords
N-phosphorylationantibodies
haptens
phosphoarginine
phosphonate amidine
Biochemistry
Enzymes and Coenzymes
Medicinal-Pharmaceutical Chemistry
Therapeutics
Metadata
Show full item recordAbstract
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.Source
Angew Chem Int Ed Engl. 2015 Oct 12. doi: 10.1002/anie.201506737. [Epub ahead of print] Link to article on publisher's siteDOI
10.1002/anie.201506737Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49981PubMed ID
26458230Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1002/anie.201506737