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

被引：73

作者：

Dal Piaz, Fabrizio ^{[1
,6
]}

Vera Saltos, Mariela Beatriz ^{[2
]}

Franceschelli, Silvia ^{[1
]}

Forte, Giovanni ^{[1
]}

Marzocco, Stefania ^{[1
]}

Tuccinard, Tiziano ^{[3
]}

Poli, Giulio ^{[3
]}

Ebrahimi, Sarnad Nejad ^{[4
]}

Hamburger, Matthias ^{[5
]}

De Tommasi, Nunziatina ^{[1
]}

Braca, Alessandra ^{[3
]}

机构：

[1] Univ Salerno, Dipartimento Farm, Via Giovanni Paolo 2 132, I-84084 Fisciano, SA, Italy

[2] Univ Fuerzas Armadas, Dept Ciencias Vida, ESPE, Ave Gen Ruminahui S-N, Sangolqui, Ecuador

[3] Univ Pisa, Dipartimento Farm, Via Bonanno 33, I-56126 Pisa, Italy

[4] Shahid Beheshti Univ, Med Plants & Drugs Res Inst, Dept Phytochem, GC, Tehran, Iran

[5] Univ Basel, Div Pharmaceut Biol, Dept Pharmaceut Sci, Basel, Switzerland

[6] Univ Salerno, Dipartimento Med Chirurg & Odontoiatria, Scuola Medica Salernitana, Via Giovanni Paolo 2, I-84084 Fisciano, SA, Italy

来源：

JOURNAL OF NATURAL PRODUCTS | 2016年 / 79卷 / 10期

关键词：

MACROCYCLIC DITERPENES; LATHYRANE DITERPENES; EUPHORBIA; LATEX;

D O I：

10.1021/acs.jnatprod.6b00627

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

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.

引用

页码：2681 / 2692

页数：12

共 40 条

[1]

[Anonymous], MAESTRO VERSION 9 0

[2]

[Anonymous], 2009, MACROMODEL VERSION 9

[3]

[Anonymous], 2013, SPECDIS VERSION 1 61

[4] Effects of diterpenes from latex of Euphorbia lactea and Euphorbia laurifolia on human immunodeficiency virus type 1 reactivation [J].