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Mar. Drugs 2017, 15(10), 312; doi:10.3390/md15100312

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

1
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Salerno, Italy
2
PhD Program in Drug Discovery and Development; University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Salerno, Italy
3
Department of Pharmacy, University of Naples “Federico II”, 80131 Naples, Italy
*
Authors to whom correspondence should be addressed.
Received: 28 July 2017 / Revised: 29 September 2017 / Accepted: 9 October 2017 / Published: 13 October 2017
(This article belongs to the Special Issue Target Identification of Marine Products)
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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. View Full-Text
Keywords: marine bioactive compounds; target identification; affinity chromatography; DARTS (drug affinity responsive target stability) marine bioactive compounds; target identification; affinity chromatography; DARTS (drug affinity responsive target stability)
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Morretta, E.; Esposito, R.; Festa, C.; Riccio, R.; Casapullo, A.; Monti, M.C. Discovering the Biological Target of 5-epi-Sinuleptolide Using a Combination of Proteomic Approaches. Mar. Drugs 2017, 15, 312.

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