Mixed Aryl Phosphonate Prodrugs of a Butyrophilin Ligand

  • ACS Med Chem Lett. 2017 Aug 9;8(9):914-918. doi: 10.1021/acsmedchemlett.7b00245.
Benjamin J Foust  1 ,  Michael M Poe  2 ,  Nicholas A Lentini  1 ,  Chia-Hung Christine Hsiao  2 ,  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.
PMID: 28947936 DOI: 10.1021/acsmedchemlett.7b00245
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.
Products