Formation and detection of oxidant-generated tryptophan dimers in peptides and proteins

Carroll, Luke; Pattison, David I.; Davies, Justin; Anderson, Robert F.; López-Alarcón, Camilo; Davies, Michael J.

doi:10.1016/j.freeradbiomed.2017.09.020

Cited by 57 publications

(43 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…59 We also suggested that environmental factors, such as UV light and solar irradiation, were also likely to favor Trp-Trp formation, 21 also in line with recent studies. 22,24,60 These recent studies argues for the importance of Trp-Trp and Trp-Tyr cross-links in protein dysfunction, oligomerization and aggregation, demanding further studies on the subject.…”

Section: Discussionsupporting

confidence: 87%

“…25 This study was just published. 59 Concomitantly, other investigators 60 showed that UV-A photolysis sensitized by kynurenic acid of N-acetyl-tryptophan under anaerobic conditions led to the formation of three types of Trp-Trp dimers (characterized by different UV spectra and MS fragmentation patterns) and possibly their diasteroisomers. These very recent results pose even more difficulties to the challenge of characterizing the structures of Trp-Trp cross-links produced in proteins by radical mechanisms.…”

Section: On the Structure Of Trp-trp Cross-links Produced By Radical mentioning

confidence: 93%

“…Davies and co-workers 25,59 showed the formation of multiple Trp-Trp dimers also in lysozyme submitted to oxidants, particularly to CO 3…”

Section: On the Structure Of Trp-trp Cross-links Produced By Radical mentioning

confidence: 99%

“…Davies and co-workers 25,59 showed the formation of multiple Trp-Trp dimers also in lysozyme submitted to oxidants, particularly to CO 3 •− , and digested by alkaline hydrolysis to release the cross-links. These results indicate that different Trp-Trp cross-links can be produced in proteins, despite the constraints imposed by the polypeptide chain and the three dimensional protein structure.…”

Section: On the Structure Of Trp-trp Cross-links Produced By Radical mentioning

confidence: 99%

“…In this case, the dimer would be the 3,4'-ditryptophan. The fact is that the full spectroscopic characterization of Trp-Trp cross-links remains to be performed and radiolysis of Trp-containing peptides may provide sufficient amounts of dimers to this purpose.Davies and co-workers 25,59 showed the formation of multiple Trp-Trp dimers also in lysozyme submitted to oxidants, particularly to CO 3•− , and digested by alkaline hydrolysis to release the cross-links. These results indicate that different Trp-Trp cross-links can be produced in proteins, despite the constraints imposed by the polypeptide chain and the three dimensional protein structure.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Ditryptophan Cross-Links as Novel Products of Protein Oxidation

Paviani

Galdino

Prazeres

et al. 2017

J. Braz. Chem. Soc.

View full text Add to dashboard Cite

Protein oxidation is an unavoidable consequence of aerobic metabolism. The oxidation of most proteins residues is non-repairable and may affect protein structure and function. In particular, protein cross-links arising from oxidative modifications are presumably toxic to cells because they may accumulate and induce protein aggregation. However, most of these irreversible protein cross-links remain partially characterized. Up to very recently, ditryptophan cross-links (Trp-Trp), in particular, have been largely disregarded in the literature. Here, we briefly review studies showing that Trp-Trp cross-links can be formed in proteins exposed to a variety of oxidants. The challenges to fully characterize Trp-Trp cross-links are discussed as well as their potential roles in protein dysfunction and aggregation.Keywords: ditryptophan, cross-links, protein oxidation, free radicals Protein OxidationFree radicals and other oxidants are formed in living organisms by oxidation-reduction processes, which occur continuously during metabolism and through interactions with the environment. Organisms evolved enzymatic antioxidant defenses and the capability to use antioxidants from the diet to control the levels of these species. 1,2 Nevertheless, under certain circumstances, the levels of radicals and oxidants increase, promoting the oxidation of biomolecules. Among them, proteins are the major targets, due to their high biological abundance and reactivity towards one-and two-electron oxidants. [3][4][5] Protein residues most susceptible to oxidation are the sulfur-containing residues Cys and Met, and the aromatic residues His, Phe, Tyr, and Trp. In vivo, the oxidation of Cys and Met residues can be reversed by biological reductants with the assistance of enzymatic systems. In fact, the reversible oxidation of protein-Cys residues is emerging as a fundamental cell regulatory mechanism. 2,[6][7][8] The oxidation of all the other protein residues is irreversible, and includes several covalent modifications, such as protein cleavage, carbonylation, nitration, hydroxylation, halogenation and protein cross-linking with other proteins, lipids, carbohydrates and nucleic acids. [3][4][5][9][10][11] These modifications result in protein fragmentation, loss of protein function, protein aggregation and/or altered protein turnover, leading to cell and tissue dysfunction and various human pathologies. To maintain cellular homeostasis, proteins irreversibly oxidized are targeted for degradation by the proteasomal and lysosomal degradation pathways.11,12 During aging and pathological conditions associated with oxidative stress, however, the levels of over-oxidized and cross-linked proteins accumulate because these species are poor substrates for the intracellular proteolytic systems. This may lead to protein aggregation, which is a hallmark of age-related diseases, such as neurodegenerative diseases, atherosclerosis and cataract.11,12 Therefore, the study of irreversible protein oxidation in vitro and in vivo is relevant to the understanding o...

show abstract

Section: Discussionsupporting

confidence: 87%

Section: On the Structure Of Trp-trp Cross-links Produced By Radical mentioning

confidence: 93%

“…Davies and co-workers 25,59 showed the formation of multiple Trp-Trp dimers also in lysozyme submitted to oxidants, particularly to CO 3…”

Section: On the Structure Of Trp-trp Cross-links Produced By Radical mentioning

confidence: 99%

Section: On the Structure Of Trp-trp Cross-links Produced By Radical mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Ditryptophan Cross-Links as Novel Products of Protein Oxidation

Paviani

Galdino

Prazeres

et al. 2017

J. Braz. Chem. Soc.

View full text Add to dashboard Cite

show abstract

Die Chemie der Proteinoxidation in Lebensmitteln

Hellwig

2019

Angewandte Chemie

View full text Add to dashboard Cite

Die Oxidation ist eine der Abbaureaktionen von Proteinen in Lebensmitteln, deren Bedeutung nicht hinter der von anderen wie der Maillard‐Reaktion, Lipierung oder Protein‐Phenol‐Reaktionen zurückbleibt. Während die Untersuchung der Proteinoxidation zu einem vertieften Verständnis der Prozesse in physiologischen Systemen geführt hat, ist das Wissen über spezifische Auswirkungen der Proteinoxidation in Lebensmitteln oder die Rolle “oxidierter” Lebensmittelproteine für den menschlichen Körper vergleichsweise gering. Oxidationsreaktionen an Lebensmittelproteinen können während des gesamten Verarbeitungsprozesses stattfinden – von der Primärproduktion bis zur Verdauung im Darm. In dem vorliegenden Aufsatz soll das derzeitige Wissen über die Mechanismen der Oxidation von Lebensmittelproteinen aus chemischer, technologischer und ernährungsphysiologischer Sicht zusammengefasst und eine Klassifizierung der einzelnen Reaktionen vorgenommen werden. Verschiedene analytische Ansätze werden verglichen, und der Zusammenhang zwischen der Oxidation von Lebensmittelproteinen und oxidativem Stress in vivo wird kritisch bewertet.

show abstract

The Chemistry of Protein Oxidation in Food

2019

View full text Add to dashboard Cite

Oxidation is one of the deterioration reactions of proteins in food, the importance of which is comparable to others such as Maillard, lipation, or protein‐phenol reactions. While research on protein oxidation has led to a precise understanding of the processes and consequences in physiological systems, knowledge about the specific effects of protein oxidation in food or the role of “oxidized” dietary protein for the human body is comparatively scarce. Food protein oxidation can occur during the whole processing axis, from primary production to intestinal digestion. The present review summarizes the current knowledge and mechanisms of food protein oxidation from a chemical, technological, and nutritional–physiological viewpoint and gives a comprehensive classification of the individual reactions. Different analytical approaches are compared, and the relationship between oxidation of food proteins and oxidative stress in vivo is critically evaluated.

show abstract

Formation and detection of oxidant-generated tryptophan dimers in peptides and proteins

Cited by 57 publications

References 67 publications

Ditryptophan Cross-Links as Novel Products of Protein Oxidation

Ditryptophan Cross-Links as Novel Products of Protein Oxidation

Die Chemie der Proteinoxidation in Lebensmitteln

The Chemistry of Protein Oxidation in Food

Contact Info

Product

Resources

About