Discovering the Biological Target of 5-epi-Sinuleptolide Using a Combination of Proteomic Approaches.

Abstract

Sinuleptolide and its congeners are diterpenes with a norcembranoid skeleton isolated from the soft coral genus Sinularia. These marine metabolites are endowed with relevant biological activities, mainly associated with cancer development. 5-epi-sinuleptolide has been selected as a candidate for target discovery studies through the application of complementary proteomic approaches. Specifically, a combination of conventional chemical proteomics based on affinity chromatography, coupled with high-resolution mass spectrometry and bioinformatics, as well as drug affinity responsive target stability (DARTS), led to a clear identification of actins as main targets for 5-epi-sinuleptolide. Subsequent in-cell assays, performed with cytochalasin D as reference compound, gave information on the ability of 5-epi-sinuleptolide to disrupt the actin cytoskeleton by loss of actin fibers and formation of F-actin amorphous aggregates. These results suggest the potential application of 5-epi-sinuleptolide as a useful tool in the study of the molecular processes impaired in several disorders in which actin is thought to play an essential role.

• Authors: Elva Morretta, Roberta Esposito, Carmen Festa, Raffaele Riccio, Agostino Casapullo, Maria Chiara Monti
• Journal: Marine drugs (Mar Drugs) Vol. 15 Issue 10 (Oct 13 2017) ISSN: 1660-3397 [Electronic] Switzerland
• PMID: 29027931 (Publication Type: Comparative Study, Journal Article)

Chemical References

• 5-episinuleptolide
• Actins
• Diterpenes
• Cytochalasin D

Topics

• Actin Cytoskeleton (drug effects, metabolism)
• Actins (metabolism)
• Animals
• Anthozoa (metabolism)
• Chromatography, Affinity (methods)
• Cytochalasin D (pharmacology)
• Diterpenes (isolation & purification, pharmacology)
• HeLa Cells
• Humans
• Mass Spectrometry (methods)
• Proteomics (methods)