Chemoselective probes for metabolite enrichment and profiling

Chemoselective probes for metabolite enrichment and profiling
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DOI:
10.1038/nmeth1038
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发表时间:
2007-05-01
期刊:
影响因子:
48
通讯作者:
Cravatt, Benjamin F.
Cravatt, Benjamin F.
中科院分区:
生物学1区
文献类型:
--
作者:
Carlson, Erin E.;Cravatt, Benjamin F.

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Chemical probes that target classes of proteins based on shared functional properties have emerged as powerful tools for proteomics. The metabolome rivals, if not surpasses, the proteome in terms of size and complexity, suggesting that efforts to profile metabolites would also benefit from targeted technologies. Here we apply the principle of chemoselective probes to the metabolome, creating a general strategy to tag, enrich and profile large classes of small molecules from biological systems. Key to success was incorporation of a protease- cleavage step to release captured metabolites in a format compatible with liquid chromatography-mass spectrometry (LC-MS) analysis. This technology, termed metabolite enrichment by tagging and proteolytic release (METPR), is applicable to small molecules of any physicochemical class, including polar, labile and low-mass (< 100 Da) compounds. We applied METPR to profile changes in the thiol metabolome of human cancer cells treated with the antioxidant N-acetyl-L-cysteine.