MALDI-MS Patterning of Caspase Activities and Its Application in the Assessment of Drug Resistance

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• 作者：Junjie Hu ; Fei Liu and Prof. Huangxian Ju
• 刊名：Angewandte Chemie
• 出版年：2016
• 出版时间：June 1, 2016
• 年：2016
• 卷：128
• 期：23
• 页码：6779-6782
• 全文大小：2154K
• ISSN：1521-3757

文摘

Mass spectrometry (MS) has been widely used for enzyme activity assays. Herein, we propose a MALDI-MS patterning strategy for the convenient visual presentation of multiple enzyme activities with an easy-to-prepare chip. The array-based caspase-activity patterned chip (Casp-PC) is fabricated by hydrophobically assembling different phospholipid-tagged peptide substrates on a modified ITO slide. The advantages of amphipathic phospholipids lead to high-quality mass spectra for imaging analysis. Upon the respective cleavage of these substrates by different caspases, such as caspase-1, -2, -3, and -8, to produce a mass shift, the enzyme activities can be directly evaluated by MALDI-MS patterning by m/z-dependent imaging of the cleavage products. The ability to identify drug-sensitive/resistant cancer cells and assess the curative effects of anticancer drugs is demonstrated, indicating the applicability of the method and the designed chip.