Document Detail

One-electron oxidation of beta-amyloid peptide: sequence modulation of reactivity.
MedLine Citation:
PMID:  15706662     Owner:  NLM     Status:  MEDLINE    
Amyloid beta peptide (Abeta) is a 39 to 43 amino-acid-long peptide implicated in Alzheimer's disease. One of its mechanisms of toxicity is related to its redox properties. Therefore we studied its one electron oxidation using azide free radicals produced in gamma and pulse radiolysis, and compared the results with those obtained with the reverse sequence Abeta(40-1). HPLC analysis combined with absorption, fluorescence, Raman spectroscopy, and MALDI-TOF MS were used for product identification. Met35 was shown to be the target in Abeta(1-40); oxidation leads to a major compound that is Abeta with methionine sulfoxide. Similarly, oxidation of fragment Abeta(29-40) also leads to methionine sulfoxide. For Abeta(40-1), Met35 is not reactive and Tyr10 is the target of azide radicals. The major products are peptide dimer linked by dityrosine and trimer. The lowering of the one-electron reduction potential of the MetS+/Met couple, which was proposed, is in agreement with our findings. To our knowledge, this is the first time that such a drastic effect of the primary sequence is observed in a small peptide. In addition, it is also the first experimental demonstration of the sensitivity of the one-electron reduction potential of methionine on neighboring groups.
Vojtech Kadlcik; Cecile Sicard-Roselli; Tony A Mattioli; Milan Kodicek; Chantal Houee-Levin
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Free radical biology & medicine     Volume:  37     ISSN:  0891-5849     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2005-02-11     Completed Date:  2005-02-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  881-91     Citation Subset:  IM    
Laboratoire de Chimie Physique, UMR 8000, Université Paris-Sud, 91405 Orsay Cedex, France.
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MeSH Terms
Alzheimer Disease / pathology*
Amino Acid Sequence
Amyloid beta-Protein / chemistry*
Azides / pharmacology
Chromatography, High Pressure Liquid
Dose-Response Relationship, Radiation
Electrophoresis, Polyacrylamide Gel
Free Radicals
Gamma Rays
Hydrogen Peroxide / chemistry,  pharmacology
Mass Spectrometry
Methionine / analogs & derivatives*,  chemistry
Models, Chemical
Molecular Sequence Data
Oxygen / chemistry
Peptide Fragments / chemistry*
Peptides / chemistry
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Spectrum Analysis, Raman
Trypsin / pharmacology
Tyrosine / analogs & derivatives*,  chemistry
Reg. No./Substance:
0/Amyloid beta-Protein; 0/Azides; 0/Free Radicals; 0/Ions; 0/Peptide Fragments; 0/Peptides; 454-41-1/methionine sulfoxide; 55520-40-6/Tyrosine; 63-68-3/Methionine; 7722-84-1/Hydrogen Peroxide; 7782-44-7/Oxygen; 980-21-2/dityrosine; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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