Document Detail


Reactions of beta-propiolactone with nucleobase analogues, nucleosides, and peptides: implications for the inactivation of viruses.
MedLine Citation:
PMID:  21868382     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
β-Propiolactone is often applied for inactivation of viruses and preparation of viral vaccines. However, the exact nature of the reactions of β-propiolactone with viral components is largely unknown. The purpose of the current study was to elucidate the chemical modifications occurring on nucleotides and amino acid residues caused by β-propiolactone. Therefore, a set of nucleobase analogues was treated with β-propiolactone, and reaction products were identified and quantified. NMR revealed at least one modification in either deoxyguanosine, deoxyadenosine, or cytidine after treatment with β-propiolactone. However, no reaction products were found from thymidine and uracil. The most reactive sides of the nucleobase analogues and nucleosides were identified by NMR. Furthermore, a series of synthetic peptides was used to determine the conversion of reactive amino acid residues by liquid chromatography-mass spectrometry. β-Propiolactone was shown to react with nine different amino acid residues. The most reactive residues are cysteine, methionine, and histidine and, to a lesser degree, aspartic acid, glutamic acid, tyrosine, lysine, serine, and threonine. Remarkably, cystine residues (disulfide groups) do not react with β-propiolactone. In addition, no reaction was observed for β-propiolactone with asparagine, glutamine, and tryptophan residues. β-Propiolactone modifies proteins to a larger extent than expected from current literature. In conclusion, the study determined the reactivity of β-propiolactone with nucleobase analogues, nucleosides, and amino acid residues and elucidated the chemical structures of the reaction products. The study provides detailed knowledge on the chemistry of β-propiolactone inactivation of viruses.
Authors:
Joost P Uittenbogaard; Bert Zomer; Peter Hoogerhout; Bernard Metz
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-08-25
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  286     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-17     Completed Date:  2011-12-07     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  36198-214     Citation Subset:  IM    
Affiliation:
Unit Vaccinology, National Institute for Public Health and the Environment, 3720 BA Bilthoven, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Disinfectants / chemistry*
Nucleosides / chemistry*
Peptides / chemistry*
Propiolactone / chemistry*
Viral Proteins / chemistry*
Virus Inactivation*
Viruses / chemistry*
Chemical
Reg. No./Substance:
0/Disinfectants; 0/Nucleosides; 0/Peptides; 0/Viral Proteins; 57-57-8/Propiolactone
Comments/Corrections

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