Selective reaction of glycine residues in hydrogen atom transfer from amino acid derivatives

Burgess, Vicky A.; Easton, Christopher J.; Hay, Michael P.

doi:10.1021/ja00185a039

Cited by 76 publications

(50 citation statements)

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“…We have re-assessed the fragment size data obtained by Schuessler and co-workers from BSA, haemoglobin and myoglobin [109,114,115], and conclude that they can be explained more readily by cleavage at glycine (M. J. Davies, unpublished work), whose α-carbon radical is especially stable [121]. Glycine residues also appear to be important in the fragmentation of calf skin collagen induced by a xanthine oxidase system [122].…”

Section: Features Of Radical-mediated Protein Fragmentation and Polymmentioning

confidence: 87%

Biochemistry and pathology of radical-mediated protein oxidation

Dean

Stocker

et al. 1997

Biochemical Journal

1,549

982

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Radical-mediated damage to proteins may be initiated by electron leakage, metal-ion-dependent reactions and autoxidation of lipids and sugars. The consequent protein oxidation is O2-dependent, and involves several propagating radicals, notably alkoxyl radicals. Its products include several categories of reactive species, and a range of stable products whose chemistry is currently being elucidated. Among the reactive products, protein hydroperoxides can generate further radical fluxes on reaction with transition-metal ions; protein-bound reductants (notably dopa) can reduce transition-metal ions and thereby facilitate their reaction with hydroperoxides; and aldehydes may participate in Schiff-base formation and other reactions. Cells can detoxify some of the reactive species, e.g. by reducing protein hydroperoxides to unreactive hydroxides. Oxidized proteins are often functionally inactive and their unfolding is associated with enhanced susceptibility to proteinases. Thus cells can generally remove oxidized proteins by proteolysis. However, certain oxidized proteins are poorly handled by cells, and together with possible alterations in the rate of production of oxidized proteins, this may contribute to the observed accumulation and damaging actions of oxidized proteins during aging and in pathologies such as diabetes, atherosclerosis and neurodegenerative diseases. Protein oxidation may also sometimes play controlling roles in cellular remodelling and cell growth. Proteins are also key targets in defensive cytolysis and in inflammatory self-damage. The possibility of selective protection against protein oxidation (antioxidation) is raised.

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Section: Features Of Radical-mediated Protein Fragmentation and Polymmentioning

confidence: 87%

Biochemistry and pathology of radical-mediated protein oxidation

Dean

Stocker

et al. 1997

Biochemical Journal

1,549

982

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“…An attempt to selectively brominate Nbenzoylvaline methyl ester in the presence of the corresponding glycine derivative resulted in preferential reaction of the glycine derivative. 17,18 A similar selectivity for reaction of glycine derivatives had been observed previously in biochemical systems 19 and through EPR studies of reactions of peptides and proteins, 20 and it had been exploited by Elad et al, [21][22][23][24][25] in the selective free radical alkylation of glycine residues in peptides and proteins. Reactions of this type occur without racemisation of other amino acid residues, which can therefore act as chiral auxiliaries in the production of the new chiral centre at the αcarbon of the glycine residue (Scheme 1).…”

Section: Regioselective Free Radical Functionalisation Of Amino Acid mentioning

confidence: 60%

“…17,18 Stabilisation of the amino acid radicals 9 and 10 will result from overlap of their semioccupied p-orbitals with the πorbitals of the amido and carboxy substituents. There will be maximum overlap of these orbitals in planar conformations of the radicals 9 and 10 ( Figure 1).…”

Section: Regioselective Free Radical Functionalisation Of Amino Acid mentioning

confidence: 99%

Recent Developments in the Use of N-Phthaloyl-Amino Acid Derivatives in Synthesis

Easton¹,

Hutton²

1998

Synlett

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“…c Corresponds to loss of 50% of the catalytic activity of PAM in processing the substrate (R)-tyrosyl-(S)-valylglycine at a concentration of 0. relative rates of consumption of 1a-8a from mixtures. 37,38,44 Since the reactions involve radical bromination, with hydrogen atom transfer from the carbon adjacent to the ester group of each substrate determining the relative rate at which that compound is brominated, the relative rates of reaction correspond to the relative ease of formation of the radicals 1c-8c.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of Peptidylglycine α-Amidating Monooxygenase by Exploitation of Factors Affecting the Stability and Ease of Formation of Glycyl Radicals

et al. 2004

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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.

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Selective reaction of glycine residues in hydrogen atom transfer from amino acid derivatives

Cited by 76 publications

References 0 publications

Biochemistry and pathology of radical-mediated protein oxidation

Biochemistry and pathology of radical-mediated protein oxidation

Recent Developments in the Use of N-Phthaloyl-Amino Acid Derivatives in Synthesis

Inhibition of Peptidylglycine α-Amidating Monooxygenase by Exploitation of Factors Affecting the Stability and Ease of Formation of Glycyl Radicals

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