Effects of Structure on <sup>α</sup>C−H Bond Enthalpies of Amino Acid Residues:  Relevance to H Transfers in Enzyme Mechanisms and in Protein Oxidation

Rauk, Arvi; Yu, Dake; Taylor, Jared M.; Shustov, G. V.; Block, and D. A.; Armstrong, David A.

doi:10.1021/bi990249x

Cited by 152 publications

(171 citation statements)

References 36 publications

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“…This captodatively-stabilized radical can then abstract the ␤-hydrogen from tyrosine through a kinetically favorable six-membered transition-state. Comparison of the calculated C-H BDEs for glycine (350 kJ/mol) and the ␤-hydrogens of tyrosine (367 kJ/mol) reveals that this abstraction is energetically feasible (⌬BDE ϭ 17 kJ/mol) [20,23]. This mechanism may access either the C-or N-terminal residue through a six-membered transitionstate.…”

Section: Resultsmentioning

confidence: 99%

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Tracking radical migration in large hydrogen deficient peptides with covalent labels: Facile movement does not equal indiscriminate fragmentation

Julian

2009

J. Am. Soc. Mass Spectrom.

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Photodissociation of iodo-tyrosine modified peptides yields localized radicals on the tyrosine side chain, which can be further dissociated by collisional activation. We have performed extensive experiments on model peptides, RGYALG, RGYG, and their derivatives, to elucidate the mechanisms underlying backbone fragmentation at tyrosine. Neither acetylation nor deuteration of the tyrosyl phenolic hydrogen significantly affects backbone fragmentation. However, deuterium migration from the tyrosyl ␤ carbon is concomitant with cleavage at tyrosine. Substitution of tyrosine with 4-hydroxyphenylglycine, which does not have ␤ hydrogens, results in almost complete elimination of backbone fragmentation at tyrosine. These results suggest that a radical situated on the ␤ carbon is required for a-type fragmentation in hydrogen-deficient radical peptides. Replacement of the ␣H of the residue adjacent to tyrosine with methyl groups results in significant diminution of backbone fragmentation. The initial radical abstracts an ␣H from the adjacent amino acid, which is poised to "rebound" and abstract the ␤H of tyrosine through a six-membered transition-state. Subsequent ␤-scission leads to the observed a-type backbone fragment. These results from deuterated peptides clearly reveal that radical migration in peptides can occur and that multiple migrations are not infrequent. Counterintuitively, close examination of all experimental results reveals that the probability for fragmentation at a particular residue is well correlated with thermodynamic radical stability. A-type fragmentation therefore appears to be most likely when favorable thermodynamics are combined with the relevant kinetic control. These results are consistent with ab initio calculations, which demonstrate that barriers to migration are significantly smaller in magnitude than probable dissociation thresholds. (J Am Soc

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Section: Resultsmentioning

confidence: 99%

“…Typical C-H BDEs in the remaining peptide are much lower. For example, the ␣C-H BDEs have been calculated to be in the range of 316 -369 kJ/mol [23]. Thus, abstraction of a hydrogen atom by the initial tyrosyl radical will be exothermic for all non aromatic hydrogens, in some cases by a significant amount.…”

mentioning

confidence: 99%

Tracking radical migration in large hydrogen deficient peptides with covalent labels: Facile movement does not equal indiscriminate fragmentation

Julian

2009

J. Am. Soc. Mass Spectrom.

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“…The reason for this structural change is a matter of speculation, but it may be that the Cterminal lanthionine bridge opened because of a captured electron and then recombined with another radical site. [34].äTheäconformationäof the diradical ions is very important for bringing two radical sites in a reactive configuration. If the radical sites are not mobile, the rate of conformational changes and thermal structure fluctuations would be the limiting factors in the rate of radical recombination into two-electron bonds.…”

Section: Resultsmentioning

confidence: 99%

Does double electron capture lead to the formation of biradicals? An ECD-SORI-CID study on lacticin 481

Kleinnijenhuis

Heck

Duursma

et al. 2005

J. Am. Soc. Mass Spectrom.

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We studied lacticin 481, a small lantibiotic with three lanthionine bridges, by electron capture dissociation (ECD) in a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. Following electron capture, very little fragmentation was observed, but species formed by nondissociative single and multiple electron capture were abundant. Ions formed by double electron capture were subjected to sustained off resonance irradiation collision induced dissociation (SORI-CID) to determine whether stable biradicals were formed. In the SORI-CID spectra of the ions formed by double electron capture, some, but minor, H• radical loss was observed, which was not observed at all for regularly protonated ions. A small part of the ions formed by double electron capture are thus long-lived biradicals. Apart from the observed H • loss, the SORI-CID spectra of ions that captured two electrons was similar to that of regularly protonated ions and quite different from the SORI-CID spectra of radical ions formed by single electron capture. This implies that recombination of the two radical sites is the dominant process in biradical lacticin 481 ions, at least on the time scale of our SORI-CID experiments. (J Am Soc Mass Spectrom 2005, 16, 1595-1601

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“…It is useful, therefore, to look at the difference in enthalpies of bond formation for the deoxyribose C-H bonds and the protein C-H, N-H or O-H bonds. While the energies of the C-H bonds in the aliphatic chain of the Lys or Arg side chains in PL or PR, respectively, are supposed to be rather high, the theoretically calculated energy of the α-C-H bond in a peptide with a Lys or Arg side chain is as low as ~340 kJ/mol (50). This is lower than the weakest of C-H deoxyribose bonds, C1′-H, which is ~376 kJ/mol according to the theoretical calculations of Miaskiewicz and Osman (51).…”

Section: Pcp Repairs Free Radical Damage On the Dna Sugar Moiety By Dmentioning

confidence: 99%

Protection of DNA against Direct Radiation Damage by Complex Formation with Positively Charged Polypeptides

2006

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Radioprotection of DNA from direct-type radiation damage by histones has been studied in model systems using complexes of positively charged polypeptides (PCPs) with DNA. PCPs bind to DNA via ionic interactions mimicking the mode of DNA-histone binding. Direct radiation damage to DNA in films of DNA-PCP complexes was quantified as unaltered base release, which correlates closely with DNA strand breaks. All types of PCPs tested protected DNA from radiation, with the maximum radioprotection being approximately 2.5-fold compared with non-complexed DNA. Conformational changes of the DNA induced by PCPs or repair of free radical damage on the DNA sugar moiety by PCPs are considered the most feasible mechanisms of radioprotection of DNA. The degree of radioprotection of DNA by polylysine (PL) increased dramatically on going from pure DNA to a molar ratio of PL monomer:DNA nucleotide ~1:2, while a further increase in the PL:DNA ratio did not offer more radioprotection. This concentration dependence is in agreement with the model of PCP binding to DNA that assumes preferential binding of positively charged side groups to DNA phosphates in the minor groove, so that the maximum occupancy of all minor-groove PCP binding sites is at a molar ratio of PCP:DNA = 1:2.

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Effects of Structure on ^αC−H Bond Enthalpies of Amino Acid Residues: Relevance to H Transfers in Enzyme Mechanisms and in Protein Oxidation

Cited by 152 publications

References 36 publications

Tracking radical migration in large hydrogen deficient peptides with covalent labels: Facile movement does not equal indiscriminate fragmentation

Tracking radical migration in large hydrogen deficient peptides with covalent labels: Facile movement does not equal indiscriminate fragmentation

Does double electron capture lead to the formation of biradicals? An ECD-SORI-CID study on lacticin 481

Protection of DNA against Direct Radiation Damage by Complex Formation with Positively Charged Polypeptides

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Effects of Structure on αC−H Bond Enthalpies of Amino Acid Residues: Relevance to H Transfers in Enzyme Mechanisms and in Protein Oxidation

Cited by 152 publications

References 36 publications

Tracking radical migration in large hydrogen deficient peptides with covalent labels: Facile movement does not equal indiscriminate fragmentation

Tracking radical migration in large hydrogen deficient peptides with covalent labels: Facile movement does not equal indiscriminate fragmentation

Does double electron capture lead to the formation of biradicals? An ECD-SORI-CID study on lacticin 481

Protection of DNA against Direct Radiation Damage by Complex Formation with Positively Charged Polypeptides

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Effects of Structure on ^αC−H Bond Enthalpies of Amino Acid Residues: Relevance to H Transfers in Enzyme Mechanisms and in Protein Oxidation