Novel pyridinium-based tags: synthesis and characterization for highly efficient analysis of thiol-containing peptides by mass spectrometry

Abstract

In this study, a novel type of pyridinium-based tags, 1-[3-[(2-iodo-1-oxoethyl)amino]propyl]-4-methylpyridinium bromide (IMP) and 1-[3-[(2-iodo-1-oxoethyl)amino]propyl]-4-propylpyridinium bromide (IPP), were designed, synthesized, and applied to the derivatization of thiol-containing peptides. With model peptides as the sample, the labeling efficiency and the stability of the peptide derivatives were investigated. The results indicate that nearly 100% derivatization yield was achieved with the developed tags and the peptide derivatives were stable at room temperature for at least one week. Furthermore, improved ionization efficiency and increased charge states were achieved via both matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) and electrospray ionization (ESI) MS, of which IPP exhibited the more obvious improvement of ionization efficiency. Further analysis of tryptic digests of bovine serum albumin (BSA) and α-transferrin, showed that increased identification efficiency of the thiol-containing peptides was achieved by combination with IMP or IPP derivatization. For example, the identification efficiency of the thiol-containing peptides of α-transferrin increased more than 42% upon combination with the IMP or IPP derivatives. We anticipate the novel tags are promising for highly efficient thiol-containing peptide identification in proteome research, especially for low concentrations.

A Novel Bisquaternary Ammonium Compound as an Anion Sensor—ESI-MS and Fluorescence Study

“…Additionally, the ionization efficiency of certain compounds during the ESI-MS experiment is low, and its reliable identification of trace amounts is restricted. The application of fixed charge tags such as quaternary ammonium (QAT) [ 14 ], phosphonium [ 15 ] and sulphonium [ 16 ] salts is one of the most important approaches for increasing ionization efficiency and detection sensitivity. Recently, we developed a quaternary ammonium fixed charge tag for sensitive peptide detection by the LC–ESI-MS/MS method.…”

Approaches to Improve the Quantitation of Oxytocin in Human Serum by Mass Spectrometry

“…When using electrospray ionization MS (ESI-MS), the sensitivity relies heavily on the analyte’s ionization efficiency and ion transmission ( Kebarle and Tang, 1993 ; Page et al, 2007 ). These factors can be improved by introducing derivatizations to the peptide such as hydrophobic and charged amino acids, as well as quaternary ammonium, phosphonium, imidazolium and pyridinium salts ( Bąchor et al, 2014 ; Qiao et al, 2014 ; Qiao et al, 2015 ; Waliczek et al, 2016 ).…”