Potent double prodrug forms of synthetic phosphoantigens.

ABSTRACT: Phosphoantigens are ligands of BTN3A1 that stimulate anti-cancer functions of γδ T cells, yet the potency of natural phosphoantigens is limited by low cell permeability and low metabolic stability. Derivatives of BTN3A1 ligand prodrugs were synthesized that contain an acetate-protected allylic alcohol and act as doubly protected prodrugs. A novel set of phosphonates, phosphoramidates, and phosphonamidates has been prepared through a new route that simplifies synthesis and postpones the point of divergence into different prodrug forms. One of the new prodrugs, compound 11, potently stimulates γδ T cell proliferation (72 h EC₅₀ = 0.12 nM) and interferon γ response to loaded leukemia cells (4 h EC₅₀ = 19 nM). This phosphonamidate form was > 900x more potent than the corr

SUBMITTER: Harmon NM 

PROVIDER: S-EPMC9491366 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature