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
Morretta E.;Tosco A.;Festa C.;Monti M. C.;
2020
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.