Live-cell Imaging Analysis of Antimycin-Type Depsipeptides via Bioorthogonal Stimulated Raman Scattering Microscopy

Small-molecule natural products have been an essential source of pharmaceuticals to treat human diseases, but very little is known about their behavior inside dynamic, living human cells. Here, we demonstrate the first structure-activity-distribution study of complex natural products, the anti-cancer antimycin-type depsipeptides, using the emerging bioorthogonal Stimulated Raman Scattering (SRS) Microscopy. Our results show that the intracellular enrichment and distribution of these compounds are driven by their potency and specific protein targets, as well as the lipophilic nature of compounds.