Q-VD-OPh, a broad spectrum caspase inhibitor with potent antiapoptotic properties
Q-VD-OPh, a broad spectrum caspase inhibitor with potent antiapoptotic properties
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DOI：
10.1023/a:1024116916932
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发表时间：
2003-08-01
期刊：
影响因子：
7.2
通讯作者：
Brown, TL
中科院分区：
文献类型：
--
作者：
Caserta, TM;Smith, AN;Brown, TL
近年来，出现了几种阻止caspase激活和凋亡的抑制剂。然而，在高剂量时，这些抑制剂可能具有非特异性作用和/或具有细胞毒性。在这项研究中，我们确定了广谱caspase抑制剂防止细胞凋亡的有效性。羧基末端的苯氧基结合氨基酸缬氨酸和天冬氨酸（Q-VD-OPh）有效地抑制细胞凋亡。Q-VD-OPh对细胞凋亡的抑制作用明显优于目前广泛应用的抑制剂zad -fmk和Boc-D-fmk，并且对caspase 9/3、caspase 8/10和caspase 12三种主要凋亡通路介导的细胞凋亡也同样有效。除了提高有效性外，即使在极高浓度下，Q-VD-OPh对细胞也没有毒性。我们的数据表明，使用羧基端邻苯氧基可以显著增强caspase抑制剂的特异性、有效性和降低毒性，并且可能在体内具有重要用途。
In recent years, several inhibitors that prevent caspase activation and apoptosis have emerged. At high doses, however, these inhibitors can have nonspecific effects and/or become cytotoxic. In this study, we determined the effectiveness of broad spectrum caspase inhibitors to prevent apoptosis. A carboxy terminal phenoxy group conjugated to the amino acids valine and aspartate (Q-VD-OPh) potently inhibited apoptosis. Q-VD-OPh was significantly more effective in preventing apoptosis than the widely used inhibitors, ZVAD-fmk and Boc-D-fmk, and was also equally effective in preventing apoptosis mediated by the three major apoptotic pathways, caspase 9/3, caspase 8/10, and caspase 12. In addition to the increased effectiveness, Q-VD-OPh was not toxic to cells even at extremely high concentrations. Our data indicate that the specificity, effectiveness, and reduced toxicity of caspase inhibitors can be significantly enhanced using carboxyterminal o-phenoxy groups and may have important uses in vivo.