Dimethyl isotope labeling assisted de novo peptide sequencing

peer-reviewed · Journal of the American Society for Mass Spectrometry · 2010

peer-reviewed · Journal of the American Society for Mass Spectrometry · 2010. Marco L. Hennrich et al. Here, we explore a de novo sequencing strategy in which we combine Lys-N protein digestion with differential…
Date 2010-12-01
Type peer-reviewed
Venue Journal of the American Society for Mass Spectrometry
Publisher American Chemical Society (ACS)
Contribution adjacent
DOI 10.1016/j.jasms.2010.08.007
Citations (OpenAlex) 27
Venue 2-year citedness 2.58

Abstract

Here, we explore a de novo sequencing strategy in which we combine Lys-N protein digestion with differential isotopic dimethyl labeling to facilitate the (de novo) identification of multiply charged peptides in ESI-MS, both under CID and ETD conditions. For a large fraction of the Lys-N generated peptides, all primary amines are present at the N-terminal lysine, enabling specific labeling of the N-terminus. Differential derivatization of only the peptide N-terminus in combination with the simultaneous fragmentation of the corresponding isotopologues allows the straightforward distinction of N-terminal fragments from C-terminal and internal fragments. Furthermore, also singly and multiply charged N-terminal fragments can easily be distinguished due to the mass differences of the isotope labeled fragment pairs. As a proof of concept, we applied this approach to proteins isolated from an avocado fruit, and were able to partially de novo sequence and correctly align, with green plant homologues, a previously uncharacterized avocado ascorbate peroxidase.

Authors

  1. Marco L. Hennrich · Netherlands Proteomics Centre, Utrecht University
  2. Shabaz Mohammed · Netherlands Proteomics Centre, Utrecht University
  3. A. F. Maarten Altelaar · Netherlands Proteomics Centre, Utrecht University
  4. Albert J. R. Heck · Center for Biomedical Genetics, Netherlands Proteomics Centre, Utrecht University

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