Monitoring the synthetic reaction of a polyamide/peptide conjugate using electrospray ionization mass spectrometry

Abstract

Recently, the chemical structures of a series of monoimidazole/polyamine conjugates were studied in this laboratory using electrospray ionization mass spectrometry (ESI-MS) combined with tandem mass spectrometry (ESI-MS/MS). The method was found to be a powerful tool for the identification of this class of compounds. During the synthesis of targeted polyamide/peptide conjugates as derivatives or analogues of netropsin and distamycin, the method was applied to analyze and track the coupling reaction for the formation of the polyamide, which was difficult to achieve using thin layer chromatography (TLC). Characteristic fragmentation pathways for a nitro-monoimidazole conjugate, an amino-monoimidazole conjugate, and the final product (a nitro-diimidazole conjugate) were explored. The fragmentations of these conjugates were strongly affected by the presence of an amino group instead of a nitro group in the molecule, and led to the identification of the three compounds in the reacting solution or in the final reaction mixture. Consequently, the reaction could be monitored successfully and the synthetic route optimized. Copyright (C) 2003 John Wiley Sons, Ltd.