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【Nature Methods编译】新的体内活性探针可以使活细
Activity probe for in vivo profiling of the specificity of proteasome inhibitor bortezomib
来源
Nature Methods 2, 357 - 362 (2005)
Published online: 21 April 2005; | doi:10.1038/nmeth759
http://www.nature.com/nmeth/journal/v2/n5/abs/nmeth759.html
摘要原文
Proteasome inhibitors, such as the dipeptide boronic acid bortezomib, are emerging as important tools in the treatment of the fatal hematologic malignancy multiple myeloma. Despite the recent US Food and Drug Administration approval of bortezomib (PS341, Velcade) for the treatment of refractory multiple myeloma, many of the basic pharmacologic parameters of bortezomib and its mode of action on myeloma cells remain to be determined. We describe the synthesis and use of a cell-permeant active site−directed probe, which allows profiling of proteasomal activities in living cells. When we compared proteasome activity patterns in cultured cells and crude cell extracts with this probe, we observed substantial differences, stressing the importance for bioassays compatible with live cells to ensure accuracy of such measurements. Using this probe, we investigated the in vivo subunit specificities of bortezomib and another inhibitor, MG132.
编译
蛋白酶抑制剂，例如 bortezomib，在治疗胎儿血液恶性多发骨髓瘤中是重要的药物。尽管最近美国FDA批准 bortezomib作为治疗顽固性多发骨髓瘤的药物，但 bortezomib的很多药理学参数以及它作用于骨髓瘤细胞的方式还有待阐明。研究者利用一个细胞活性渗透位点作为直接探针，以此能够在活细胞中检测蛋白酶体的活性。当用这个探针比较培养的细胞和粗提取细胞的蛋白酶体活性时，研究者观察到了很多的不同，主要是它可以用于活细胞生物鉴定并能确保方法的准确性。利用这个探针，我们研究了特内亚基特异性的 bortezomib 和另一个蛋白酶体抑制剂 MG132。 [标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-04-25 05:14
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