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Screening Method for the Discovery of Potential Bioactive Cysteine-Containing Peptides Using 3D Mass Mapping.

van Oosten, Luuk N; Pieterse, Mervin; Pinkse, Martijn W H and Verhaert, Peter LU (2015) In Journal of the American Society for Mass Spectrometry 26(12). p.2039-2050
Abstract
Animal venoms and toxins are a valuable source of bioactive peptides with pharmacologic relevance as potential drug leads. A large subset of biologically active peptides discovered up till now contain disulfide bridges that enhance stability and activity. To discover new members of this class of peptides, we developed a workflow screening specifically for those peptides that contain inter- and intra-molecular disulfide bonds by means of three-dimensional (3D) mass mapping. Two intrinsic properties of the sulfur atom, (1) its relatively large negative mass defect, and (2) its isotopic composition, allow for differentiation between cysteine-containing peptides and peptides lacking sulfur. High sulfur content in a peptide decreases the... (More)
Animal venoms and toxins are a valuable source of bioactive peptides with pharmacologic relevance as potential drug leads. A large subset of biologically active peptides discovered up till now contain disulfide bridges that enhance stability and activity. To discover new members of this class of peptides, we developed a workflow screening specifically for those peptides that contain inter- and intra-molecular disulfide bonds by means of three-dimensional (3D) mass mapping. Two intrinsic properties of the sulfur atom, (1) its relatively large negative mass defect, and (2) its isotopic composition, allow for differentiation between cysteine-containing peptides and peptides lacking sulfur. High sulfur content in a peptide decreases the normalized nominal mass defect (NMD) and increases the normalized isotopic shift (NIS). Hence in a 3D plot of mass, NIS, and NMD, peptides with sulfur appear in this plot with a distinct spatial localization compared with peptides that lack sulfur. In this study we investigated the skin secretion of two frog species; Odorrana schmackeri and Bombina variegata. Peptides from the crude skin secretions were separated by nanoflow LC, and of all eluting peptides high resolution zoom scans were acquired in order to accurately determine both monoisotopic mass and average mass. Both the NMD and the NIS were calculated from the experimental data using an in-house developed MATLAB script. Candidate peptides exhibiting a low NMD and high NIS values were selected for targeted de novo sequencing, and this resulted in the identification of several novel inter- and intra-molecular disulfide bond containing peptides. Graphical Abstract ᅟ. (Less)
Please use this url to cite or link to this publication:
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organization
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type
Contribution to journal
publication status
published
subject
in
Journal of the American Society for Mass Spectrometry
volume
26
issue
12
pages
2039 - 2050
publisher
Elsevier
external identifiers
  • pmid:26552389
  • wos:000365116500008
  • scopus:84947547908
ISSN
1879-1123
DOI
10.1007/s13361-015-1282-z
language
English
LU publication?
yes
id
6c967478-f5b9-48bb-9b89-46ee9f43caae (old id 8236210)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26552389?dopt=Abstract
date added to LUP
2015-12-03 20:15:43
date last changed
2017-01-01 03:24:45
@article{6c967478-f5b9-48bb-9b89-46ee9f43caae,
  abstract     = {Animal venoms and toxins are a valuable source of bioactive peptides with pharmacologic relevance as potential drug leads. A large subset of biologically active peptides discovered up till now contain disulfide bridges that enhance stability and activity. To discover new members of this class of peptides, we developed a workflow screening specifically for those peptides that contain inter- and intra-molecular disulfide bonds by means of three-dimensional (3D) mass mapping. Two intrinsic properties of the sulfur atom, (1) its relatively large negative mass defect, and (2) its isotopic composition, allow for differentiation between cysteine-containing peptides and peptides lacking sulfur. High sulfur content in a peptide decreases the normalized nominal mass defect (NMD) and increases the normalized isotopic shift (NIS). Hence in a 3D plot of mass, NIS, and NMD, peptides with sulfur appear in this plot with a distinct spatial localization compared with peptides that lack sulfur. In this study we investigated the skin secretion of two frog species; Odorrana schmackeri and Bombina variegata. Peptides from the crude skin secretions were separated by nanoflow LC, and of all eluting peptides high resolution zoom scans were acquired in order to accurately determine both monoisotopic mass and average mass. Both the NMD and the NIS were calculated from the experimental data using an in-house developed MATLAB script. Candidate peptides exhibiting a low NMD and high NIS values were selected for targeted de novo sequencing, and this resulted in the identification of several novel inter- and intra-molecular disulfide bond containing peptides. Graphical Abstract ᅟ.},
  author       = {van Oosten, Luuk N and Pieterse, Mervin and Pinkse, Martijn W H and Verhaert, Peter},
  issn         = {1879-1123},
  language     = {eng},
  number       = {12},
  pages        = {2039--2050},
  publisher    = {Elsevier},
  series       = {Journal of the American Society for Mass Spectrometry},
  title        = {Screening Method for the Discovery of Potential Bioactive Cysteine-Containing Peptides Using 3D Mass Mapping.},
  url          = {http://dx.doi.org/10.1007/s13361-015-1282-z},
  volume       = {26},
  year         = {2015},
}