A Photoalkylative Fluorogenic Probe of Guttiferone A for Live Cell Imaging and Proteome Labeling in .

Guttiferone A (GA) , a polycyclic polyprenylated acylphloroglucinol (PPAP) isolated from the plant (Clusiaceae), constitutes a novel hit in antimalarial drug discovery. PPAPs do not possess identified biochemical targets in malarial parasites up to now. Towards this aim, we designed and evaluated a natural product-derived photoactivatable probe AZC-GA , embedding a photoalkylative fluorogenic motif of the 7-azidocoumarin (AZC) type, devoted to studying the affinity proteins interacting with GA in . Probe manifested a number of positive functional and biological features, such as (i) inhibitory activity in vitro against blood-stages that was superimposable to that of GA , dose-response photoalkylative fluorogenic properties (ii) in model conditions using bovine serum albumin (BSA) as an affinity protein surrogate, (iii) in live -infected erythrocytes, and (iv) in fresh cell lysate. Fluorogenic signals by photoactivated AZC-GA in biological settings were markedly abolished in the presence of excess GA as a competitor, indicating significant pharmacological specificity of the designed molecular probe relative to the native PPAP. These results open the way to identify the detected plasmodial proteins as putative drug targets for the natural product by means of proteomic analysis.