Reactions of beta-propiolactone with nucleobase analogues, nucleosides, and peptides: implications for the inactivation of viruses.

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Uittenbogaard JP, Zomer B, Hoogerhout P, Metz B

Reactions of beta-propiolactone with nucleobase analogues, nucleosides, and peptides: implications for the inactivation of viruses.

J Biol Chem. 2011 Oct 21;286(42):36198-214. doi: 10.1074/jbc.M111.279232. Epub 2011 Aug 25.

PubMed ID
21868382 [ View in PubMed
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Abstract

beta-Propiolactone is often applied for inactivation of viruses and preparation of viral vaccines. However, the exact nature of the reactions of beta-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 beta-propiolactone. Therefore, a set of nucleobase analogues was treated with beta-propiolactone, and reaction products were identified and quantified. NMR revealed at least one modification in either deoxyguanosine, deoxyadenosine, or cytidine after treatment with beta-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. beta-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 beta-propiolactone. In addition, no reaction was observed for beta-propiolactone with asparagine, glutamine, and tryptophan residues. beta-Propiolactone modifies proteins to a larger extent than expected from current literature. In conclusion, the study determined the reactivity of beta-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 beta-propiolactone inactivation of viruses.

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