Mixed Aryl Phosphonate Prodrugs of a Butyrophilin Ligand

Benjamin J Foust; Michael M Poe; Nicholas A Lentini; Chia-Hung Christine Hsiao; Andrew J Wiemer; David F Wiemer

doi:10.1021/acsmedchemlett.7b00245

Mixed Aryl Phosphonate Prodrugs of a Butyrophilin Ligand

ACS Med Chem Lett. 2017 Aug 9;8(9):914-918. doi: 10.1021/acsmedchemlett.7b00245. eCollection 2017 Sep 14.

Authors

Benjamin J Foust¹, Michael M Poe², Nicholas A Lentini¹, Chia-Hung Christine Hsiao², Andrew J Wiemer^{2

3}, David F Wiemer^{1

4}

Affiliations

¹ Department of Chemistry, University of Iowa, Iowa City, Iowa 52242-1294, United States.
² Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut 06269-3092 United States.
³ Institute for Systems Genomics, University of Connecticut, Storrs, Connecticut 06269-3092, United States.
⁴ Department of Pharmacology, University of Iowa, Iowa City, Iowa 52242-1109, United States.

Abstract

Studies of aryl phosphonate derivatives of a butyrophilin 3A1 ligand have resulted in identification of a potent stimulant of Vγ9 Vδ2 T cells. This compound, a mixed ester bearing one pivaloyloxymethyl substituent and one 1-naphthyl ester displayed an EC₅₀ of 0.79 nM as a stimulant of T cell proliferation, and a 9.0 nM EC₅₀ in an assay designed to measure interferon gamma production. In both assays, this is the most potent butyrophilin ligand prodrug yet reported, and thus it should be a valuable tool for studies of T cell function. Furthermore, mixed aryl/acyloxyalkyl esters may represent a new class of phosphonate prodrugs with high efficacy.

Keywords: Aryl phosphonates; BTN3A1; butyrophilin; ligand; phosphoantigen; prodrug.

Abstract

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