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

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Crellastatin A, a PARP-1 Inhibitor Discovered by Complementary Proteomic Approaches.
ChemMedChem ( IF 3.6 ) Pub Date : 2019-12-12 , DOI: 10.1002/cmdc.201900634
Elva Morretta _{1,

2} , Alessandra Tosco ₁ , Carmen Festa ₃ , Matteo Mozzicafreddo ₄ , Maria C Monti ₁ , Agostino Casapullo ₁

Affiliation

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.

中文翻译：

Crellastatin A，一种通过互补蛋白质组学方法发现的PARP-1抑制剂。

Crellastatin A是一种从瓦努阿图岛海洋海绵Crella sp。中分离出来的具有细胞毒性的硫酸化双类固醇，被选为有趣的探针，用于针对蛋白质相互作用的特性进行全面的蛋白质组学分析。鉴于其独特的结构特征，A进行了基于质谱的药物亲和响应靶标稳定性（DARTS）分析，并结合了（靶向限制性蛋白水解多反应监测（t-LiP MRM），而不是经典的亲和纯化策略。聚ADP-核糖聚合酶-1（PARP-1）成为主要的crellastatin A细胞伴侣，这一结果已被生化分析和计算机分析证实，进一步的体外生物学分析突显了crellastatin A对PARP-的抑制作用。 1。

更新日期：2020-01-08

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