Generation of stable isopentenyl monophosphate aryloxy triester phosphoramidates as activators of Vγ9Vδ2 T cells

Xu, Qin, Taher, Taher E., Ashby, Elizabeth, Sharif, Maria, Willcox, Benjamin E. and Mehellou, Youcef ORCID: https://orcid.org/0000-0001-5720-8513 2021. Generation of stable isopentenyl monophosphate aryloxy triester phosphoramidates as activators of Vγ9Vδ2 T cells. ChemMedChem 16 (15) , pp. 2375-2380. 10.1002/cmdc.202100198

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Abstract

Aryloxy triester phosphoramidate prodrugs of the monophosphate derivatives of isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) were synthesized as lipophilic derivatives that can improve cell uptake. Despite the structural similarity of IPP and DMAPP, it was noted that their phosphoramidate prodrugs exhibited distinct stability profiles in aqueous environments, which we show is due to the position of the allyl bond in the backbones of the IPP and DMAPP monophosphates. As the IPP monophosphate aryloxy triester phosphoramidates showed favorable stability, they were subsequently investigated for their ability to activate Vγ9/Vδ2 T cells and they showed promising activation of this subset of T cells. Together, these findings represent the first report of IPP and DMAPP monophosphate prodrugs and the ability of IPP aryloxy triester phosphoramidate prodrugs to activate Vγ9/Vδ2 T cells highlighting their potential as possible immunotherapeutics.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Additional Information:	The Authors. ChemMedChem published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License
Publisher:	Wiley
ISSN:	1860-7179
Date of First Compliant Deposit:	30 April 2021
Date of Acceptance:	21 April 2021
Last Modified:	23 May 2023 13:28
URI:	https://orca.cardiff.ac.uk/id/eprint/140886

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