Document Detail

Rapid sensitive analysis of cysteine rich peptide venom components.
MedLine Citation:
PMID:  19380747     Owner:  NLM     Status:  MEDLINE    
Disulfide-rich peptide venoms from animals such as snakes, spiders, scorpions, and certain marine snails represent one of nature's great diversity libraries of bioactive molecules. The various species of marine cone shells have alone been estimated to produce >50,000 distinct peptide venoms. These peptides have stimulated considerable interest because of their ability to potently alter the function of specific ion channels. To date, only a small fraction of this immense resource has been characterized because of the difficulty in elucidating their primary structures, which range in size between 10 and 80 aa, include up to 5 disulfide bonds, and can contain extensive posttranslational modifications. The extraordinary complexity of crude venoms and the lack of DNA databases for many of the organisms of interest present major analytical challenges. Here, we describe a strategy that uses mass spectrometry for the elucidation of the mature peptide toxin components of crude venom samples. Key to this strategy is our use of electron transfer dissociation (ETD), a mass spectrometric fragmentation technique that can produce sequence information across the entire peptide backbone. However, because ETD only yields comprehensive sequence coverage when the charge state of the precursor peptide ion is sufficiently high and the m/z ratio is low, we combined ETD with a targeted chemical derivatization strategy to increase the charge state of cysteine-containing peptide toxins. Using this strategy, we obtained full sequences for 31 peptide toxins, using just 7% of the crude venom from the venom gland of a single cone snail (Conus textile).
Beatrix M Ueberheide; David Fenyö; Paul F Alewood; Brian T Chait
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-04-20
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  106     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-05-06     Completed Date:  2009-06-05     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6910-5     Citation Subset:  IM    
Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA.
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MeSH Terms
Amino Acid Sequence
Cysteine / analysis,  chemistry
DNA, Complementary / genetics
Databases, Genetic
Mass Spectrometry / methods*
Models, Molecular
Molecular Sequence Data
Peptides / analysis*,  chemistry*,  genetics
Sensitivity and Specificity
Structural Homology, Protein
Time Factors
Venoms / analysis*,  chemistry*,  genetics
Grant Support
Reg. No./Substance:
0/DNA, Complementary; 0/Peptides; 0/Venoms; 52-90-4/Cysteine

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