Inhibition of peptidylglycine alpha-amidating monooxygenase by exploitation of factors affecting the stability and ease of formation of glycyl radicals

Barratt, B, Easton, C, Henry, D, Li, I, Radom, L and Simpson, J 2004, 'Inhibition of peptidylglycine alpha-amidating monooxygenase by exploitation of factors affecting the stability and ease of formation of glycyl radicals', Journal of the American Chemical Society, vol. 126, no. 41, pp. 13306-13311.


Document type: Journal Article
Collection: Journal Articles

Title Inhibition of peptidylglycine alpha-amidating monooxygenase by exploitation of factors affecting the stability and ease of formation of glycyl radicals
Author(s) Barratt, B
Easton, C
Henry, D
Li, I
Radom, L
Simpson, J
Year 2004
Journal name Journal of the American Chemical Society
Volume number 126
Issue number 41
Start page 13306
End page 13311
Total pages 6
Publisher American Chemical Society
Abstract Peptidylglycine alpha-amidating monooxygenase catalyzes the biosynthesis of peptide hormones through radical cleavage of the C-terminal glycine residues of the corresponding prohormones. We have correlated ab initio calculations of radical stabilization energies and studies of free radical brominations with the extent of catalysis displayed by peptidylglycine alpha-amidating monooxygenase, to identify classes of inhibitors of the enzyme. In particular we find that, in closely related systems, the substitution of glycolate for glycine reduces the calculated radical stabilization energy by 34.7 kJ mol -1, decreases the rate of bromination with N-bromosuccinimide at reflux in carbon tetrachloride by a factor of at least 2000, and stops catalysis by the monooxygenase, while maintaining binding to the enzyme.
Subject Reaction Kinetics and Dynamics
Chemical Thermodynamics and Energetics
DOI - identifier 10.1021/ja046204n
ISSN 1089-5639
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