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Mixed Aryl Phosphonate Prodrugs of a Butyrophilin Ligand
Journal article   Open access   Peer reviewed

Mixed Aryl Phosphonate Prodrugs of a Butyrophilin Ligand

Benjamin J Foust, Michael M Poe, Nicholas A Lentini, Chia-Hung Christine Hsiao, Andrew J Wiemer and David F Wiemer
ACS Medicinal Chemistry Letters, Vol.8(9), pp.914-918
2017
DOI: 10.1021/acsmedchemlett.7b00245
PMCID: PMC5601366
PMID: 28947936
url
https://doi.org/10.1021/acsmedchemlett.7b00245View
Published (Version of record) Open Access

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 EC 50 of 0.79 nM as a stimulant of T cell proliferation, and a 9.0 nM EC 50 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.
prodrug BTN3A1 Aryl phosphonates ligand butyrophilin phosphoantigen

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