Superoxide radicals react with peptide-derived tryptophan radicals with very high rate constants to give hydroperoxides as major products.

Show simple item record Carroll, Luke Pattison, David I Davies, Justin B Anderson, Robert F Lopez-Alarcon, Camilo Davies, Michael J
dc.coverage.spatial United States 2020-12-08T23:48:25Z 2020-12-08T23:48:25Z 2018-4
dc.identifier.issn 0891-5849
dc.description.abstract Oxidative damage is a common process in many biological systems and proteins are major targets for damage due to their high abundance and very high rate constants for reaction with many oxidants (both radicals and two-electron species). Tryptophan (Trp) residues on peptides and proteins are a major sink for a large range of biological oxidants as these side-chains have low radical reduction potentials. The resulting Trp-derived indolyl radicals (Trp•) have long lifetimes in some circumstances due to their delocalized structures, and undergo only slow reaction with molecular oxygen, unlike most other biological radicals. In contrast, we have shown previously that Trp• undergo rapid dimerization. In the current study, we show that Trp• also undergo very fast reaction with superoxide radicals, O2•-, with k 1-2 × 109 M-1 s-1. These values do not alter dramatically with peptide structure, but the values of k correlate with overall peptide positive charge, consistent with positive electrostatic interactions. These reactions compete favourably with Trp• dimerization and O2 addition, indicating that this may be a major fate in some circumstances. The Trp• + O2•- reactions occur primarily by addition, rather than electron transfer, with this resulting in high yields of Trp-derived hydroperoxides. Subsequent degradation of these species, both stimulated and native decay, gives rise to N-formylkynurenine, kynurenine, alcohols and diols. These data indicate that reaction of O2•- with Trp• should be considered as a major pathway to Trp degradation on peptides and proteins subjected to oxidative damage.
dc.format.medium Print-Electronic
dc.language eng
dc.publisher Elsevier BV
dc.relation.ispartofseries Free radical biology & medicine
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher.
dc.subject Hydrogen Peroxide
dc.subject Superoxides
dc.subject Free Radicals
dc.subject Tryptophan
dc.subject Peptides
dc.subject Oxidation-Reduction
dc.subject Oxidative Stress
dc.subject Dimerization
dc.subject Hydroperoxide
dc.subject Kynurenine
dc.subject N-formylkynurenine
dc.subject Protein oxidation
dc.subject Superoxide
dc.subject Tryptophan
dc.subject Science & Technology
dc.subject Life Sciences & Biomedicine
dc.subject Biochemistry & Molecular Biology
dc.subject Endocrinology & Metabolism
dc.subject Protein oxidation
dc.subject Tryptophan
dc.subject Superoxide
dc.subject Hydroperoxide
dc.subject Dimerization
dc.subject N-formylkynurenine
dc.subject Kynurenine
dc.subject SIDE-CHAIN
dc.subject AMINO-ACID
dc.subject 0305 Organic Chemistry
dc.subject Basic Science
dc.subject 0304 Medicinal and Biomolecular Chemistry
dc.subject 0601 Biochemistry and Cell Biology
dc.subject 1101 Medical Biochemistry and Metabolomics
dc.title Superoxide radicals react with peptide-derived tryptophan radicals with very high rate constants to give hydroperoxides as major products.
dc.type Journal Article
dc.identifier.doi 10.1016/j.freeradbiomed.2018.02.033
pubs.begin-page 126
pubs.volume 118 2020-11-16T18:59:04Z
dc.rights.holder Copyright: The author en
pubs.end-page 136
pubs.publication-status Published
dc.rights.accessrights en
pubs.subtype Research Support, Non-U.S. Gov't
pubs.subtype Journal Article
pubs.elements-id 728238
dc.identifier.eissn 1873-4596
dc.identifier.pii S0891-5849(18)30090-X

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