These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
HMBP_Kadri_Preprint_F.pdf (1.99 MB)
Aryloxy Triester Phosphonamidates of Phosphoantigens Exhibit Favorable Stability and Potent Activation of Vγ9/Vδ2 T‐Cells
Preprints are manuscripts made publicly available before they have been submitted for formal peer review and publication. They might contain new research findings or data. Preprints can be a draft or final version of an author's research but must not have been accepted for publication at the time of submission.
submitted on 06.07.2018 and posted on 06.07.2018by Hachemi Kadri, Taher E. Taher, Qin Xu, Richard T. Bryan, Benjamin E. Willcox, Youcef Mehellou
We previously reported the
application of the aryloxy triester phosphoramidate prodrug technology to the
phosphoantigen (E)-4-hydroxybut-2-enyl phosphate (HMBP). Although these prodrugs
exhibited potent activation of Vγ9/Vδ2 T‐cell immune responses, their stability
was low due to the rapid cleavage of the -O-P- bond. To address this, we herein
report the application of the same prodrug strategy to two HMBP phosphonates,
which have stable -CH2-P- or -CF2-P- bonds. These HMBP phosphonate prodrugs,
phosphonamidates, exhibited excellent serum stability and potent activation of
Vgama9/Vdelta2 T‐cells making them attractive compounds for further development as