Drug Affinity Responsive Target Stability (DARTS) Identifies Laurifolioside as a New Clathrin Heavy Chain Modulator

作者：Dal Piaz Fabrizio; Vera Saltos Mariela Beatriz; Franceschelli Silvia; Forte Giovanni; Marzocco Stefania; Tuccinard Tiziano; Poli Giulio; Ebrahimi Sarnad Nejad; Hamburger Matthias; De Tommasi Nunziatina^*; Braca Alessandra

来源：Journal of Natural Products, 2016, 79(10): 2681-2692.

DOI：10.1021/acs.jnatprod.6b00627

Five new diterpenes (1-5) and a megastigmane derivative (6) were isolated from the aerial parts of Euphorbia laurifolia, along with several known compounds. Their structures were elucidated by NMR, MS, and ECD and by chemical methods. A chemical proteomics drug affinity responsive target stability (DARTS) approach to investigate the lathyrane diterpene 1, laurifolioside, on its putative cellular target(s) was performed. Clathrin heavy chain 1, a protein mainly involved in selective uptake of proteins, viruses, and other macromolecules at the plasma membrane of cells, was identified as the major interaction partner of compound 1. The modulation of clathrin activity by 1 was studied through microscopy, molecular docking, and molecular dynamics studies, suggesting a new activity of lathyrane diterpenes in the modulation of trafficking pathways.

• 出版日期2016-10