ER-specific localization and stress detection with phenothiazine nucleoside fluorescent probes

Abstract

We designed and synthesized two novel fluorescent nucleoside probes, purine phenothiazine (PP) and aminopurine phenothiazine (AP), to explore their potential for sub-cellular imaging. Both probes demonstrated strong cellular uptake; however, cellular imaging showed that PP, in contrast to AP, exhibited localization within the endoplasmic reticulum (ER), making it a valuable tool for studying ER-specific processes. AP, by comparison, displayed broader, less targeted organelle distribution. To assess PP’s effectiveness in detecting ER stress, COS-7 cells were exposed to nutrient starvation and tunicamycin, both established ER stress inducers. PP responded efficiently, selectively accumulating in the ER under stress conditions. This study highlights the promise of purine nucleoside derivatives as innovative tools for probing sub-cellular dynamics and expands molecular imaging resources.