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

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

  • Dal Piaz F Dipartimento di Farmacia, Università di Salerno , Via Giovanni Paolo II 132, 84084 Fisciano (SA), Italy.
  • Vera Saltos MB Departamento de Ciencias de la Vida, Universidad de las Fuerzas Armadas , ESPE, Avenida General Rumiñahui s/n, Sangolqui, Ecuador.
  • Franceschelli S Dipartimento di Farmacia, Università di Salerno , Via Giovanni Paolo II 132, 84084 Fisciano (SA), Italy.
  • Forte G Dipartimento di Farmacia, Università di Salerno , Via Giovanni Paolo II 132, 84084 Fisciano (SA), Italy.
  • Marzocco S Dipartimento di Farmacia, Università di Salerno , Via Giovanni Paolo II 132, 84084 Fisciano (SA), Italy.
  • Tuccinardi T Dipartimento di Farmacia, Università di Pisa , Via Bonanno 33, 56126 Pisa, Italy.
  • Poli G Dipartimento di Farmacia, Università di Pisa , Via Bonanno 33, 56126 Pisa, Italy.
  • Nejad Ebrahimi S Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University , G. C., Evin, Tehran, Iran.
  • Hamburger M Division of Pharmaceutical Biology, Department of Pharmaceutical Sciences, University of Basel , Basel, Switzerland.
  • De Tommasi N Dipartimento di Farmacia, Università di Salerno , Via Giovanni Paolo II 132, 84084 Fisciano (SA), Italy.
  • Braca A Dipartimento di Farmacia, Università di Pisa , Via Bonanno 33, 56126 Pisa, Italy.
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  • 2016-10-06
Published in:
  • Journal of natural products. - 2016
Clathrin Heavy Chains
Cyclohexanones
Diterpenes
Ecuador
Euphorbia
Glucosides
Humans
Molecular Docking Simulation
Molecular Structure
Norisoprenoids
Nuclear Magnetic Resonance, Biomolecular
Plant Components, Aerial
Plant Proteins
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/201757
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