Novel Quaternary Ammonium Functionaltags: Design, Synthesis And Its Application For Peptide Labeling

Chemical derivatization is widely used for increasing the detection sensitivity of protein/peptide by mass spectrometry. Recently, a variety of tags were developed and further used for increasing the ionization efficiency of peptides in mass spectrometry.In the present work, five novel quaternary ammonium functional tags designed with iodoacetamide groups were synthesyed, including 1-[3-[(2-iodo-1-oxoethyl)amino]-propyl]-4-methylpyridinium bromide(IMP), 1-[3-[(2-iodo-1-oxoethyl)amino]-propyl]-4-propylpyridinium bromide(IPP), N,N-dimethyl-N-ethyl-3-(iodoacetamide)propyl bromide(IEP), N,N-dimethyl-N-butyl-3-(iodoacetamide)propyl bromide(IBP), N,N-dimethyl-N-octyl-3-(iodoacetamide)propyl bromide(IOP).The tag IMP and IPP were further used for thiol-containing peptides derivatization and mass spectrometry analysis. Both of the two tags indicated with 100% labeling efficiency and the peptides derivatives could stabilze in the reaction buffer for at least one week. Furthermore, the ionization efficiency of the peptides derivatized by IMP or IPP via Matrix-Assisted Laser Desorption/ Ionization Time of Flight Mass Spectrometry(MALDI-TOF MS) and Electrospray ionization Mass Spectrometry(ESI MS) were largely increased. By further analysis of tyrptic digests of bovine serum albumin and α-transferrin, increased identification efficiency of thiol-containing peptides were achieved.