(A) No immunofluorescence (IF) signal was observed after incubation with negative control dioxolane compound, Diox-Puromycin, (1 μM) for 2 hr, indicating no puromycin incorporation. Strong IF signal showed after incubating cells with unconjugated puromycin in rat Schwann cells. Scale bar = 20 μm. (B) The chemical structure of TRX-puromycin labile Fe(II) probe. (C) The chemical structure of nonperoxidic dioxolane compound, Diox-Puromycin. The α-amine of puromycin is carbamoylated in both compounds. Consequently, these two conjugated compounds cannot be incorporated into nascent polypeptides, unlike unconjugated puromycin. Labile Fe(II) can react with the 1,2,4-trioxolane ring of TRX-Puromycin causing release of the puromycin and its incorporation into nascent polypeptides, which can then be detected by anti-puromycin antibody. Labile Fe(II) does not react with the bioisosteric nonperoxidic dioxolane compound, Diox-Puromycin, which was used as negative control for all labile Fe(II) IF experiments (n = 6 independent experiments with three biological replicates).