Figure 1
From: Selective Targeting of Virus Replication by Proton Pump Inhibitors
Anti-viral activity requires intracellular prodrug conversion. Panel A, Schematic showing conversion of tenatoprazole prodrug (1) to reactive sulfenic acid (2) or sulfenamide (3). Reactivity of 1 is conferred by the centrally-located sulfoxyl group (S=O) which is flanked on the right by a 2-pyridyl group and on the left by an imidazopyridine ring. Molecule 4 shows the position on the activated compound where targets with reactive SH groups (such as C73 on Tsg101, designated as R-SH), bind. Figure is adapted from Strickland et al.3 Panel B, 293 T cells were treated with DMSO (lanes 1, 5) or DMSO plus prodrug (lanes 2–4) or the acid pre-activated compound (lanes 6–8) six hours prior to transfection with DNA encoding HA-tagged HIV-1 Gag. Western blot analysis of isolated VLP (top), cell lysate Gag-HA (middle), and actin (bottom). Panel C, quantitative analysis of Top right, VLP production normalized to cellular actin; Middle, Gag accumulation in the cytoplasm, normalized to actin; Bottom, VLP release efficiency, normalized to cellular Gag accumulation plus VLP-associated Gag (i.e., VLP/(VLP + cellular Gag).
