Fragmentation and sequencing of cyclic peptides by MALDI-PSD mass spectrometry

Abstract

In spite of recent improvements in mass spectrometric techniques, determination of the amino acid sequence of cyclic peptides is not straightforward and the interpretation of fragment ion spectra is more difficult than for analogous linear peptides. Most published studies [1] used ionization methods such as FAB/liquid-assisted secondary ion mass spectrometry (LSIMS) or electrospray ionization tandem mass spectrometry (ESI MS/MS). This work represents the first systematic MALDI post source decay (MALDI-PSD) study investigating biologically relevant cyclic peptides [2]. The goal of this study was to develop an easy mass spectrometric method for structural elucidation and analysis of unknown cyclic peptides. We synthesized several cyclic decapeptides and other smaller cyclic peptides that were originally used as inhibitors of (Src) [3], a protein tyrosine kinase (PTK) that is an attractive target for anti-cancer drug design [4]. These cyclic peptides were investigated by MALDI-PSD and we were especially interested in cyclic peptide fragmentation pattern depending on the amino acid composition.