TY - JOUR

T1 - Oxidative Crosslinking of Peptides and Proteins

T2 - Mechanisms of Formation, Detection, Characterization and Quantification

AU - Fuentes-Lemus, Eduardo

AU - Hägglund, Per

AU - López-Alarcón, Camilo

AU - Davies, Michael J.

N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/1/1

Y1 - 2022/1/1

N2 - Covalent crosslinks within or between proteins play a key role in determining the structure and function of proteins. Some of these are formed intentionally by either enzymatic or molecular reactions and are critical to normal physiological function. Others are generated as a consequence of exposure to oxidants (radicals, excited states or two-electron species) and other endogenous or external stimuli, or as a result of the actions of a number of enzymes (e.g., oxidases and peroxidases). Increasing evidence indicates that the accumulation of unwanted crosslinks, as is seen in ageing and multiple pathologies, has adverse effects on biological function. In this article, we review the spectrum of crosslinks, both reducible and non-reducible, currently known to be formed on proteins; the mechanisms of their formation; and experimental approaches to the detection, identification and characterization of these species.

AB - Covalent crosslinks within or between proteins play a key role in determining the structure and function of proteins. Some of these are formed intentionally by either enzymatic or molecular reactions and are critical to normal physiological function. Others are generated as a consequence of exposure to oxidants (radicals, excited states or two-electron species) and other endogenous or external stimuli, or as a result of the actions of a number of enzymes (e.g., oxidases and peroxidases). Increasing evidence indicates that the accumulation of unwanted crosslinks, as is seen in ageing and multiple pathologies, has adverse effects on biological function. In this article, we review the spectrum of crosslinks, both reducible and non-reducible, currently known to be formed on proteins; the mechanisms of their formation; and experimental approaches to the detection, identification and characterization of these species.

KW - Aggregation

KW - Crosslink

KW - Di-tryptophan

KW - Di-tyrosine

KW - Dimerization

KW - Disulfides

KW - Mass spectrometry

KW - Protein oxidation

KW - Proteomics

KW - Radicals

KW - Thiols

UR - http://www.scopus.com/inward/record.url?scp=85122124580&partnerID=8YFLogxK

U2 - 10.3390/molecules27010015

DO - 10.3390/molecules27010015

M3 - Review

C2 - 35011250

AN - SCOPUS:85122124580

VL - 27

SP - 1

EP - 31

JO - Molecules (Print Archive Edition)

JF - Molecules (Print Archive Edition)

SN - 1431-5157

IS - 1

M1 - 15

ER -