CMP-唾液酸（CMP-Neu5Ac）的几种去磷酸化类似物作为GM3合酶抑制剂的合成及生物学评价
Synthesis and biological evaluation of several dephosphonated analogues of CMP-Neu5Ac as inhibitors of GM3-synthase.
作者信息
Rota Paola, Cirillo Federica, Piccoli Marco, Gregorio Antonio, Tettamanti Guido, Allevi Pietro, Anastasia Luigi
机构信息
Department of Biomedical, Surgical and Dental Sciences, Institution University of Milan, Via Saldini 50, 20133 Milan (Italy).
Laboratory of Stem Cells for Tissue Engineering, IRCCS Policlinico San Donato, San Donato Milanese, Milan (Italy).
出版信息
Chemistry. 2015 Oct 5;21(41):14614-29. doi: 10.1002/chem.201501770. Epub 2015 Aug 11.
Previous studies demonstrated that reducing the GM3 content in myoblasts increased the cell resistance to hypoxic stress, suggesting that a pharmacological inhibition of the GM3 synthesis could be instrumental for the development of new treatments for ischemic diseases. Herein, the synthesis of several dephosphonated CMP-Neu5Ac congeners and their anti-GM3-synthase activity is reported. Biological activity testes revealed that some inhibitors almost completely blocked the GM3-synthase activity in vitro and reduced the GM3 content in living embryonic kidney 293A cells, eventually activating the epidermal growth factor receptor (EGFR) signaling cascade.
先前的研究表明，降低成肌细胞中的GM3含量可增强细胞对缺氧应激的抗性，这表明对GM3合成进行药理学抑制可能有助于开发缺血性疾病的新疗法。本文报道了几种去磷酸化的CMP-Neu5Ac类似物的合成及其抗GM3合酶活性。生物活性测试表明，一些抑制剂在体外几乎完全阻断了GM3合酶的活性，并降低了活的胚胎肾293A细胞中的GM3含量，最终激活了表皮生长因子受体（EGFR）信号级联反应。
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