Synthesis and Biological Evaluation of (E)-4-Hydroxy-3-methylbut-2-enyl Phosphate (HMBP) Aryloxy Triester Phosphoramidate Prodrugs as Activators of Vγ9/Vδ2 T-Cell Immune Responses

被引：29

作者：

Davey, Martin S. ^{[1
,2
]}

Malde, Roshni ^{[3
]}

Mykura, Rory C. ^{[3
]}

Baker, Alfie T. ^{[1
,2
]}

Taher, Taher E. ^{[1
,2
]}

Le Duff, Cecile S. ^{[3
]}

Willcox, Benjamin E. ^{[1
,2
]}

Mehellou, Youcef ^{[4
]}

机构：

[1] Univ Birmingham, Canc Immunol & Immunotherapy Ctr, Birmingham B15 2TT, W Midlands, England

[2] Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham B15 2TT, W Midlands, England

[3] Univ Birmingham, Sch Chem, Birmingham B15 2TT, W Midlands, England

[4] Cardiff Univ, Sch Pharm & Pharmaceut Sci, Redwood Bldg, Cardiff CF10 3NB, S Glam, Wales

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2018年 / 61卷 / 05期

基金：

英国惠康基金;

关键词：

PHOSPHONATE PRODRUGS; NONPEPTIDE ANTIGENS; B30.2; DOMAIN; PHOSPHOANTIGENS; PYROPHOSPHATE; DERIVATIVES; BTN3A1; BLOOD;

D O I：

10.1021/acs.jmedchem.7b01824

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The aryloxy triester phosphoramidate prodrug approach has been used with success in drug discovery. Herein, we describe the first application of this prodrug technology to the monophosphate derivative of the phosphoantigen HMBPP and one of its analogues. Some of these prodrugs exhibited specific and potent activation of V gamma 9/V delta 2 T-cells, which were then able to lyse bladder cancer cells in vitro. This work highlights the promise of this prodrug technology in the discovery of novel immunotherapeutics.

引用

页码：2111 / 2117

页数：7

共 19 条

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Mehellou, Youcef
JOURNAL OF MEDICINAL CHEMISTRY, 2020, 63 (19) : 11258 - 11270
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[3] A Photo-Crosslinkable Biotin Derivative of the Phosphoantigen (E)-4-Hydroxy-3-Methylbut-2-Enyl Diphosphate (HMBPP) Activates Vγ9Vδ2 T Cells and Binds to the HMBPP Site of BTN3A1
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JOURNAL OF ORGANIC CHEMISTRY, 2008, 73 (04): : 1365 - 1370
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TETRAHEDRON LETTERS, 2002, 43 (14) : 2555 - 2559
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