Crellastatin A, a cytotoxic sulfated bis-steroid isolated from the Vanuatu Island marine sponge Crella sp., was selected as an interesting probe for a comprehensive proteomic analysis directed at the characterization of its protein interactors. Given its peculiar structural features, A was submitted to a mass spectrometry-based drug affinity responsive target stability (DARTS) assay combined with (targeted-limited proteolysis-multiple reaction monitoring (t-LiP MRM), rather than a classical affinity purification strategy. Poly-ADP-ribose-polymerase-1 (PARP-1) emerged as the main crellastatin A cellular partner. This result was confirmed by both biochemical and in silico analyses. Further in vitro biological assays highlighted an interesting crellastatin A inhibitory activity on PARP-1.

Crellastatin A, a PARP-1 Inhibitor Discovered by Complementary Proteomic Approaches / Morretta, E.; Tosco, A.; Festa, C.; Mozzicafreddo, M.; Monti, M. C.; Casapullo, A.. - In: CHEMMEDCHEM. - ISSN 1860-7179. - 15:3(2020), pp. 317-323. [10.1002/cmdc.201900634]

Crellastatin A, a PARP-1 Inhibitor Discovered by Complementary Proteomic Approaches

Mozzicafreddo M.;
2020-01-01

Abstract

Crellastatin A, a cytotoxic sulfated bis-steroid isolated from the Vanuatu Island marine sponge Crella sp., was selected as an interesting probe for a comprehensive proteomic analysis directed at the characterization of its protein interactors. Given its peculiar structural features, A was submitted to a mass spectrometry-based drug affinity responsive target stability (DARTS) assay combined with (targeted-limited proteolysis-multiple reaction monitoring (t-LiP MRM), rather than a classical affinity purification strategy. Poly-ADP-ribose-polymerase-1 (PARP-1) emerged as the main crellastatin A cellular partner. This result was confirmed by both biochemical and in silico analyses. Further in vitro biological assays highlighted an interesting crellastatin A inhibitory activity on PARP-1.
2020
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11566/300005
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