MMass as a Software Tool for the Annotation of Cyclic Peptide Tandem Mass Spectra

Timo H J Niedermeyer,Martin Strohalm,John Matthew Koomen

doi:10.1371/journal.pone.0044913

Abstract

Natural or synthetic cyclic peptides often possess pronounced bioactivity. Their mass spectrometric characterization is difficult due to the predominant occurrence of non-proteinogenic monomers and the complex fragmentation patterns observed. Even though several software tools for cyclic peptide tandem mass spectra annotation have been published, these tools are still unable to annotate a majority of the signals observed in experimentally obtained mass spectra. They are thus not suitable for extensive mass spectrometric characterization of these compounds. This lack of advanced and user-friendly software tools has motivated us to extend the fragmentation module of a freely available open-source software, mMass (http://www.mmass.org), to allow for cyclic peptide tandem mass spectra annotation and interpretation. The resulting software has been tested on several cyanobacterial and other naturally occurring peptides. It has been found to be superior to other currently available tools concerning both usability and annotation extensiveness. Thus it is highly useful for accelerating the structure confirmation and elucidation of cyclic as well as linear peptides and depsipeptides.

Highlights

Cyclic peptides are a group of natural products that attracts the interest of a large number of researchers due to their intriguing structures and powerful and diverse bioactivities
These compounds can be of ribosomal origin [7,8], but predominantly they are synthesized by non-ribosomal peptide synthetases (NRPS) [9,10,11,12]
Non-ribosomal peptides are fascinating for the natural product chemist, as they are composed of proteinogenic amino acids and contain unusual and highly modified amino acids or monomers constructed by polyketide synthases (PKS)

Summary

Introduction

Cyclic peptides are a group of natural products that attracts the interest of a large number of researchers due to their intriguing structures and powerful and diverse bioactivities. Non-ribosomal peptides are fascinating for the natural product chemist, as they are composed of proteinogenic amino acids and contain unusual and highly modified amino acids or monomers constructed by polyketide synthases (PKS). These compounds often derive from a mixed PKS/NRPS biosynthetic pathway as described in great detail e.g. for the cyanobacterial microcystins [13,14,15].

Methods

Results

Conclusion