title: Drug Affinity Responsive Target Stability (DARTS) Identifies Laurifolioside as a New Clathrin Heavy Chain Modulator.
abstract: 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.
authors.affiliation: Dipartimento di Farmacia, Università di Salerno , Via Giovanni Paolo II 132, 84084 Fisciano (SA), Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Dal Piaz
authors.affiliation: Departamento de Ciencias de la Vida, Universidad de las Fuerzas Armadas , ESPE, Avenida General Rumiñahui s/n, Sangolqui, Ecuador.
authors.forename: Mariela Beatriz
authors.initials: MB
authors.lastname: Vera Saltos
authors.affiliation: Dipartimento di Farmacia, Università di Salerno , Via Giovanni Paolo II 132, 84084 Fisciano (SA), Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Franceschelli
authors.affiliation: Dipartimento di Farmacia, Università di Salerno , Via Giovanni Paolo II 132, 84084 Fisciano (SA), Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Forte
authors.affiliation: Dipartimento di Farmacia, Università di Salerno , Via Giovanni Paolo II 132, 84084 Fisciano (SA), Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Marzocco
authors.affiliation: Dipartimento di Farmacia, Università di Pisa , Via Bonanno 33, 56126 Pisa, Italy.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Tuccinardi
authors.affiliation: Dipartimento di Farmacia, Università di Pisa , Via Bonanno 33, 56126 Pisa, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Poli
authors.affiliation: Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University , G. C., Evin, Tehran, Iran.
authors.forename: Samad
authors.initials: S
authors.lastname: Nejad Ebrahimi
authors.affiliation: Division of Pharmaceutical Biology, Department of Pharmaceutical Sciences, University of Basel , Basel, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hamburger
authors.affiliation: Dipartimento di Farmacia, Università di Salerno , Via Giovanni Paolo II 132, 84084 Fisciano (SA), Italy.
authors.forename: Nunziatina
authors.initials: N
authors.lastname: De Tommasi
authors.affiliation: Dipartimento di Farmacia, Università di Pisa , Via Bonanno 33, 56126 Pisa, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Braca
mesh_terms: D033922:Clathrin Heavy Chains / Q000378:metabolism*; D003512:Cyclohexanones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004484:Ecuador; D028481:Euphorbia / Q000737:chemistry*; D005960:Glucosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D045792:Norisoprenoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D019906:Nuclear Magnetic Resonance, Biomolecular; D035261:Plant Components, Aerial / Q000737:chemistry; D010940:Plant Proteins / Q000032:analysis / Q000737:chemistry
chemical_list: D003512:Cyclohexanones; D004224:Diterpenes; D005960:Glucosides; D045792:Norisoprenoids; D010940:Plant Proteins; C530347:lathyrane; C000620420:laurifolioside; C413264:megastigmane; D033922:Clathrin Heavy Chains