Leveraging Gas-Phase Fragmentation Pathways for Improved Identification and Selective Detection of Targets Modified by Covalent Probes
详细信息 查看全文
- 作者：Scott B. Ficarro ; Christopher M. Browne ; Joseph D. Card ; William M. Alexander ; Tinghu Zhang ; Eunyoung Park ; Randall McNally ; Sirano Dhe-Paganon ; Hyuk-Soo Seo ; Ilaria Lamberto ; Michael J. Eck ; Sara J. Buhrlage ; Nathanael S. Gray ; Jarrod A. Marto
- 刊名：Analytical Chemistry
- 出版年：2016
- 出版时间：December 20, 2016
- 年：2016
- 卷：88
- 期：24
- 页码：12248-12254
- 全文大小：394K
- ISSN：1520-6882
文摘
The recent approval of covalent inhibitors for multiple clinical indications has reignited enthusiasm for this class of drugs. As interest in covalent drugs has increased, so too has the need for analytical platforms that can leverage their mechanism-of-action to characterize modified protein targets. Here we describe novel gas phase dissociation pathways which yield predictable fragment ions during MS/MS of inhibitor-modified peptides. We find that these dissociation pathways are common to numerous cysteine-directed probes as well as the covalent drugs, Ibrutinib and Neratinib. We leverage the predictable nature of these fragment ions to improve the confidence of peptide sequence assignment in proteomic analyses and explore their potential use in selective mass spectrometry-based assays.