A new strategy to determine the protein mutation site using matrix-assisted laser desorption ionization in-source decay: derivatization by ionic liquid

Analytica Chimica Acta
Mengzhe GuoYuanjiang Pan

Abstract

Matrix-assisted laser desorption ionization (MALDI) time-of-flight mass spectrometry (TOF-MS) can be considered as state of the art in the field of proteins and peptides analysis. In this work, we have designed an ionic liquid derivative strategy to obtain abundant fragment ions in MALDI in-source decay (ISD) and used the analysis of angiogenin with mutation in the fortieth (K40I) as an instance. Firstly, we have synthesized two types of ionic liquids, 3-allyl-4-methyl-1H-imidazol-3-ium and 4-methyl-3-(pent-4-yn-1-yl)-1H-imidazol-3-ium. Then in the light-catalyzed reaction, the alkenyl ionic liquid can open the disulfide bond of K40I protein and add to the thiol. And the derived protein can process in-source decay under the effect of ionic liquid group to produce c-z type ions. Additionally this fragmentation is potentiated to support widely range of fragment ions which can cover the location of mutation. Our results have supplied a new top-down method about how to analyze the mutation or even post-translational modification of proteins in MALDI mass spectrometry.

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Citations

Feb 24, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hong YaoXinhua Lin
Sep 20, 2017·Journal of Separation Science·Kevin D ClarkJared L Anderson
Feb 10, 2021·Critical Reviews in Analytical Chemistry·Vladimir G Zaikin, Roman S Borisov
Oct 20, 2018·Analytical Chemistry·María J Trujillo-RodríguezJared L Anderson

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