Discovering the Biological Target of 5-epi-Sinuleptolide Using a Combination of Proteomic Approaches.
Elva MorrettaRoberta EspositoCarmen FestaRaffaele RiccioAgostino CasapulloMaria Chiara MontiPublished in: Marine drugs (2017)
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.
Keyphrases
- high resolution mass spectrometry
- liquid chromatography
- mass spectrometry
- cell migration
- papillary thyroid
- tandem mass spectrometry
- ultra high performance liquid chromatography
- stem cells
- gas chromatography
- squamous cell carcinoma
- risk assessment
- single molecule
- health information
- high speed
- emergency department
- young adults
- room temperature
- social media
- human health
- high performance liquid chromatography