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Radiation and Photochemical Modifications in Proteins: Mechanistic Aspects and Applications

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Physical Chemistry and Chemical Physics".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 21180

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Prof. Dr. Krzysztof Bobrowski

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Centre of Radiation Research and Technology, Institute of Nuclear Chemistry and Technology, Warsaw, Poland
Interests: radiation- and photo-induced radical processes in sulfur containing amino acids; peptides; nucleobases; heterocyclic compounds; long range electron transfer processes in peptides and proteins; oxidative stress; kinetics of free radicals; pulse radiolysis
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Prof. Dr. Bronisław Marciniak

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1. Faculty of Chemistry, Adam Mickiewicz University, Poznań, Poland
2. Center for Advanced Technology, Adam Mickiewicz University, Poznań, Poland
Interests: photophysics; photochemistry; radiation chemistry of organic compounds of biological interest; photo-induced chemical reactions in sulfur- or silicon-containing organic compounds of importance in biology and material chemistry
Special Issues, Collections and Topics in MDPI journals

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Dear Colleagues,

Proteins are highly abundant cellular biomolecules and therefore are a major target when biological systems are irradiated or illuminated. Radiation- and photo-induced modifications in proteins are associated with changes in their structure and functions. Radiolysis (the initiation of reactions by high-energy radiation) and photolysis (the initiations of reactions by UV and visible light) were found as very valuable and powerful chemical tools for inducing and studying radical processes that are of particular interest in biology and life sciences. The use of the methods of radiolysis and photolysis has provided a wealth of data, especially about the kinetics of the oxidation by various free radicals and their mechanisms, the identification of transients formed, their lifetimes and the possibility to repair them by the so-called antioxidants. The detailed knowledge of free radical modifications in proteins is becoming of increasing importance connected with understanding of their mechanisms in the development of damage in proteins under conditions of oxidative and reductive stress, aging, the etiology of several cardiovascular and neurodegenerative diseases and inflammation processes. The availability of time-resolved techniques, high-end technologies and detection methods to monitor single or global radiation- and photo-induced modifications of proteins has increased enormously in recent years, giving a much better insight into post-translational modification. Many final products were already demonstrated as possibly useful for biomarkers. All these data about protein modification might be helpful to a proteomic approach.

The gathered articles in these special issue are expected to provide a reference for the recent development in this interdisciplinary and practical subject to radiation- and photochemists, organic, medicinal, and pharmaco chemists, molecular modeling chemists as well as to cellular biologists who are in the target audience.

Research articles and reviews related to these topics in protein chemistry and applications are welcome.

Prof. Krzysztof Bobrowski
Prof. Bronisław Marciniak
Guest Editors

Manuscript Submission Information

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Keywords

proteins
peptides
free radicals
radiolysis
photolysis
free radicals
oxidative and reductive stress
biomarkers
antioxidants

Related Special Issue

Radiation and Photochemical Modifications in Proteins: Mechanistic Aspects and Applications 2.0 in International Journal of Molecular Sciences

Published Papers (11 papers)

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Research

Jump to: Review

33 pages, 9494 KiB

Open AccessArticle

Spontaneous and Ionizing Radiation-Induced Aggregation of Human Serum Albumin: Dityrosine as a Fluorescent Probe

by Karolina Radomska and Marian Wolszczak

Int. J. Mol. Sci. 2022, 23(15), 8090; https://doi.org/10.3390/ijms23158090 - 22 Jul 2022

Cited by 5 | Viewed by 1932

Abstract

The use of spectroscopic techniques has shown that human serum albumin (HSA) undergoes reversible self-aggregation through protein–protein interactions. It ensures the subsequent overlapping of electron clouds along with the stiffening of the conformation of the interpenetrating network of amino acids of adjacent HSA molecules. The HSA oxidation process related to the transfer of one electron was investigated by pulse radiolysis and photochemical methods. It has been shown that the irradiation of HSA solutions under oxidative stress conditions results in the formation of stable protein aggregates. The HSA aggregates induced by ionizing radiation are characterized by specific fluorescence compared to the emission of non-irradiated solutions. We assume that HSA dimers are mainly responsible for the new emission. Dityrosine produced by the intermolecular recombination of protein tyrosine radicals as a result of radiolysis of an aqueous solution of the protein is the main cause of HSA aggregation by cross-linking. Analysis of the oxidation process of HSA confirmed that the reaction of mild oxidants (

{Br}_{2}^{• -}

N_{3}^{•}

{SO}_{4}^{• -}

) with albumin leads to the formation of covalent bonds between tyrosine residues. In the case of ^•OH radicals and partly,

{Cl}_{2}^{• -}

, species other than DT are formed. The light emission of this species is similar to the emission of self-associated HSA. Full article

(This article belongs to the Special Issue Radiation and Photochemical Modifications in Proteins: Mechanistic Aspects and Applications)

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18 pages, 4899 KiB

Open AccessArticle

Evaluation of Hydroxyl Radical Reactivity by Thioether Group Proximity in Model Peptide Backbone: Methionine versus S-Methyl-Cysteine

by Chryssostomos Chatgilialoglu, Magdalena Grzelak, Konrad Skotnicki, Piotr Filipiak, Franciszek Kazmierczak, Gordon L. Hug, Krzysztof Bobrowski and Bronislaw Marciniak

Int. J. Mol. Sci. 2022, 23(12), 6550; https://doi.org/10.3390/ijms23126550 - 11 Jun 2022

Cited by 2 | Viewed by 1689

Abstract

Hydroxyl radicals (HO^•) have long been regarded as a major source of cellular damage. The reaction of HO^• with methionine residues (Met) in peptides and proteins is a complex multistep process. Although the reaction mechanism has been intensively studied, some essential parts remain unsolved. In the present study we examined the reaction of HO^• generated by ionizing radiation in aqueous solutions under anoxic conditions with two compounds representing the simplest model peptide backbone CH₃C(O)NHCHXC(O)NHCH₃, where X = CH₂CH₂SCH₃ or CH₂SCH₃, i.e., the Met derivative in comparison with the cysteine-methylated derivative. We performed the identification and quantification of transient species by pulse radiolysis and final products by LC–MS and high-resolution MS/MS after γ-radiolysis. The results allowed us to draw for each compound a mechanistic scheme. The fate of the initial one-electron oxidation at the sulfur atom depends on its distance from the peptide backbone and involves transient species of five-membered and/or six-membered ring formations with different heteroatoms present in the backbone as well as quite different rates of deprotonation in forming α-(alkylthio)alkyl radicals. Full article

(This article belongs to the Special Issue Radiation and Photochemical Modifications in Proteins: Mechanistic Aspects and Applications)

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15 pages, 14725 KiB

Open AccessArticle

Protein Dimerization via Tyr Residues: Highlight of a Slow Process with Co-Existence of Numerous Intermediates and Final Products

by Anouchka Gatin, Patricia Duchambon, Guillaume van der Rest, Isabelle Billault and Cécile Sicard-Roselli

Int. J. Mol. Sci. 2022, 23(3), 1174; https://doi.org/10.3390/ijms23031174 - 21 Jan 2022

Cited by 2 | Viewed by 1638

Abstract

Protein dimerization via tyrosine residues is a crucial process in response to an oxidative attack, which has been identified in many ageing-related pathologies. Recently, it has been found that for isolated tyrosine amino acid, dimerization occurs through three types of tyrosine–tyrosine crosslinks and leads to at least four final products. Herein, considering two protected tyrosine residues, tyrosine-containing peptides and finally proteins, we investigate the dimerization behavior of tyrosine when embedded in a peptidic sequence. After azide radical oxidation and by combining UPLC-MS and H/D exchange analyzes, we were able to evidence: (i) the slow kinetics of Michael Addition Dimers (MAD) formation, i.e., more than 48 h; (ii) the co-existence of intermediates and final cyclized dimer products; and (iii) the probable involvement of amide functions to achieve Michael additions even in proteins. This raises the question of the possible in vivo existence of both intermediates and final entities as well as their toxicity and the potential consequences on protein structure and/or function. Full article

(This article belongs to the Special Issue Radiation and Photochemical Modifications in Proteins: Mechanistic Aspects and Applications)

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13 pages, 2246 KiB

Open AccessArticle

Accumulation of Cytochrome b₅₅₈ at the Plasma Membrane: Hallmark of Oxidative Stress in Phagocytic Cells

by Stephenson B. Owusu, Sophie Dupré-Crochet, Tania Bizouarn, Chantal Houée-Levin and Laura Baciou

Int. J. Mol. Sci. 2022, 23(2), 767; https://doi.org/10.3390/ijms23020767 - 11 Jan 2022

Cited by 2 | Viewed by 1289

Abstract

Neutrophils play a very key role in the human immune defense against pathogenic infections. The predominant players in this role during the activation of neutrophils are the release of cytotoxic agents stored in the granules and secretory vesicles and the massive production of reactive oxygen species (ROS) initiated by the enzyme NADPH oxidase. In addition, in living organisms, cells are continuously exposed to endogenous (inflammations, elevated neutrophil presence in the vicinity) and exogenous ROS at low and moderate levels (travels by plane, radiotherapy, space irradiation, blood banking, etc.). To study these effects, we used ROS induced by gamma radiation from low (0.2 Gy) to high (25 Gy) dose levels on PLB-985 cells from a myeloid cell line differentiated to neutrophil-like cells that are considered a good alternative to neutrophils. We determined a much longer lifetime of PLB-985 cells than that of neutrophils, which, as expected, decreased by increasing the irradiation dose. In the absence of any secondary stimulus, a very low production of ROS is detected with no significant difference between irradiated and non-irradiated cells. However, in phagocytosing cells, irradiation doses above 2 Gy enhanced oxidative burst in PLB-985 cells. Whatever the irradiation dose, NADPH oxidase devoid of its cytosolic regulatory units is observed at the plasma membrane in irradiated PLB-985 cells. This result is different from that observed for irradiated neutrophils in which irradiation also induced a translocation of regulatory subunits suggesting that the signal transduction mechanism or pathway operate differently in both cells. Full article

(This article belongs to the Special Issue Radiation and Photochemical Modifications in Proteins: Mechanistic Aspects and Applications)

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9 pages, 1154 KiB

Open AccessArticle

Free Radical Generation in Far-UV Synchrotron Radiation Circular Dichroism Assays—Protein and Buffer Composition Contribution

by Paolo Ruzza, Claudia Honisch, Rohanah Hussain and Giuliano Siligardi

Int. J. Mol. Sci. 2021, 22(21), 11325; https://doi.org/10.3390/ijms222111325 - 20 Oct 2021

Cited by 4 | Viewed by 1638

Abstract

A useful tool to analyze the ligands and/or environmental contribution to protein stability is represented by the Synchrotron Radiation Circular Dichroism UV-denaturation assay that consists in the acquisition of several consecutive repeated far-UV SRCD spectra. Recently we demonstrated that the prevailing mechanism of this denaturation involves the generation of free radicals and reactive oxygen species (ROS). In this work, we analyzed the effect of buffering agents commonly used in spectroscopic measurements, including MOPS (3-(N-morpholino) propanesulfonic acid), HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), TRIS-HCl (tris-hydroxymethil aminomethane hydrochloride), and phosphate, on the efficiency of protein denaturation caused by exposure to UV radiation. Fluorescence experiments confirmed the presence of ROS and were used to determine the rate of ROS generation. Our results indicate that the efficiency of the denaturation process is strongly influenced by the buffer composition with MOPS and HEPES acting also as scavengers and that the presence of proteins itself influenced the ROS formation rate. Full article

(This article belongs to the Special Issue Radiation and Photochemical Modifications in Proteins: Mechanistic Aspects and Applications)

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16 pages, 2479 KiB

Open AccessArticle

Optimization of Novel Human Acellular Dermal Dressing Sterilization for Routine Use in Clinical Practice

by Hanna Lewandowska, Andrzej Eljaszewicz, Izabela Poplawska, Marlena Tynecka, Alicja Walewska, Kamil Grubczak, Jordan Holl, Hady Razak Hady, Slawomir Lech Czaban, Joanna Reszec, Grażyna Przybytniak, Wojciech Głuszewski, Jarosław Sadło, Małgorzata Dąbrowska-Gralak, Cezary Kowalewski, Piotr Fiedor, Tomasz Oldak, Artur Kaminski, Zbigniew Zimek and Marcin Moniuszko

Int. J. Mol. Sci. 2021, 22(16), 8467; https://doi.org/10.3390/ijms22168467 - 06 Aug 2021

Cited by 4 | Viewed by 1691

Abstract

Gamma rays and electrons with kinetic energy up to 10 MeV are routinely used to sterilize biomaterials. To date, the effects of irradiation upon human acellular dermal matrices (hADMs) remain to be fully elucidated. The optimal irradiation dosage remains a critical parameter affecting the final product structure and, by extension, its therapeutic potential. ADM slides were prepared by various digestion methods. The influence of various doses of radiation sterilization using a high-energy electron beam on the structure of collagen, the formation of free radicals and immune responses to non-irradiated (native) and irradiated hADM was investigated. The study of the structure changes was carried out using the following methods: immunohistology, immunoblotting, and electron paramagnetic resonance (EPR) spectroscopy. It was shown that radiation sterilization did not change the architecture and three-dimensional structure of hADM; however, it significantly influenced the degradation of collagen fibers and induced the production of free radicals in a dose-dependent manner. More importantly, the observed effects did not disrupt the therapeutic potential of the new transplants. Therefore, radiation sterilization at a dose of 35kGy can ensure high sterility of the dressing while maintaining its therapeutic potential. Full article

(This article belongs to the Special Issue Radiation and Photochemical Modifications in Proteins: Mechanistic Aspects and Applications)

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16 pages, 3288 KiB

Open AccessArticle

Radiation- and Photo-Induced Oxidation Pathways of Methionine in Model Peptide Backbone under Anoxic Conditions

by Tomasz Pędzinski, Katarzyna Grzyb, Konrad Skotnicki, Piotr Filipiak, Krzysztof Bobrowski, Chryssostomos Chatgilialoglu and Bronislaw Marciniak

Int. J. Mol. Sci. 2021, 22(9), 4773; https://doi.org/10.3390/ijms22094773 - 30 Apr 2021

Cited by 8 | Viewed by 2439

Abstract

Within the reactive oxygen species (ROS) generated by cellular metabolisms, hydroxyl radicals (HO^•) play an important role, being the most aggressive towards biomolecules. The reactions of HO^• with methionine residues (Met) in peptides and proteins have been intensively studied, but some fundamental aspects remain unsolved. In the present study we examined the biomimetic model made of Ac-Met-OMe, as the simplest model peptide backbone, and of HO^• generated by ionizing radiation in aqueous solutions under anoxic conditions. We performed the identification and quantification of transient species by pulse radiolysis and of final products by LC-MS and high-resolution MS/MS after γ-radiolysis. By parallel photochemical experiments, using 3-carboxybenzophenone (CB) triplet with the model peptide, we compared the outcomes in terms of short-lived intermediates and stable product identification. The result is a detailed mechanistic scheme of Met oxidation by HO^•, and by CB triplets allowed for assigning transient species to the pathways of products formation. Full article

(This article belongs to the Special Issue Radiation and Photochemical Modifications in Proteins: Mechanistic Aspects and Applications)

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Review

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9 pages, 1457 KiB

Open AccessReview

Advanced Oxidation Processes in Pharmaceutical Formulations: Photo-Fenton Degradation of Peptides and Proteins

by Christian Schöneich

Int. J. Mol. Sci. 2022, 23(15), 8262; https://doi.org/10.3390/ijms23158262 - 27 Jul 2022

Cited by 2 | Viewed by 1442

Abstract

Formulations of therapeutic proteins are sensitive to photo-degradation by near UV and visible light. Mechanistically, especially the processes leading to protein modification under visible light exposure are not understood. Potentially, these processes may be triggered by a ligand to metal charge transfer in excipient-metal complexes. This article summarizes recent analytical and mechanistic work on such reactions under experimental conditions relevant to pharmaceutical formulations. Full article

(This article belongs to the Special Issue Radiation and Photochemical Modifications in Proteins: Mechanistic Aspects and Applications)

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16 pages, 3368 KiB

Open AccessReview

Radiolysis Studies of Oxidation and Nitration of Tyrosine and Some Other Biological Targets by Peroxynitrite-Derived Radicals

by Lisa K. Folkes, Silvina Bartesaghi, Madia Trujillo, Peter Wardman and Rafael Radi

Int. J. Mol. Sci. 2022, 23(3), 1797; https://doi.org/10.3390/ijms23031797 - 04 Feb 2022

Cited by 6 | Viewed by 2128

Abstract

The widespread interest in free radicals in biology extends far beyond the effects of ionizing radiation, with recent attention largely focusing on reactions of free radicals derived from peroxynitrite (i.e., hydroxyl, nitrogen dioxide, and carbonate radicals). These radicals can easily be generated individually by reactions of radiolytically-produced radicals in aqueous solutions and their reactions can be monitored either in real time or by analysis of products. This review first describes the general principles of selective radical generation by radiolysis, the yields of individual species, the advantages and limitations of either pulsed or continuous radiolysis, and the quantitation of oxidizing power of radicals by electrode potentials. Some key reactions of peroxynitrite-derived radicals with potential biological targets are then discussed, including the characterization of reactions of tyrosine with a model alkoxyl radical, reactions of tyrosyl radicals with nitric oxide, and routes to nitrotyrosine formation. This is followed by a brief outline of studies involving the reactions of peroxynitrite-derived radicals with lipoic acid/dihydrolipoic acid, hydrogen sulphide, and the metal chelator desferrioxamine. For biological diagnostic probes such as ‘spin traps’ to be used with confidence, their reactivities with radical species have to be characterized, and the application of radiolysis methods in this context is also illustrated. Full article

(This article belongs to the Special Issue Radiation and Photochemical Modifications in Proteins: Mechanistic Aspects and Applications)

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15 pages, 2353 KiB

Open AccessReview

Initiation and Prevention of Biological Damage by Radiation-Generated Protein Radicals

by Janusz M. Gebicki and Thomas Nauser

Int. J. Mol. Sci. 2022, 23(1), 396; https://doi.org/10.3390/ijms23010396 - 30 Dec 2021

Cited by 7 | Viewed by 1503

Abstract

Ionizing radiations cause chemical damage to proteins. In aerobic aqueous solutions, the damage is commonly mediated by the hydroxyl free radicals generated from water, resulting in formation of protein radicals. Protein damage is especially significant in biological systems, because proteins are the most abundant targets of the radiation-generated radicals, the hydroxyl radical-protein reaction is fast, and the damage usually results in loss of their biological function. Under physiological conditions, proteins are initially oxidized to carbon-centered radicals, which can propagate the damage to other molecules. The most effective endogenous antioxidants, ascorbate, GSH, and urate, are unable to prevent all of the damage under the common condition of oxidative stress. In a promising development, recent work demonstrates the potential of polyphenols, their metabolites, and other aromatic compounds to repair protein radicals by the fast formation of less damaging radical adducts, thus potentially preventing the formation of a cascade of new reactive species. Full article

(This article belongs to the Special Issue Radiation and Photochemical Modifications in Proteins: Mechanistic Aspects and Applications)

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13 pages, 2030 KiB

Open AccessReview

Reductive Stress of Sulfur-Containing Amino Acids within Proteins and Implication of Tandem Protein–Lipid Damage

by Chryssostomos Chatgilialoglu and Carla Ferreri

Int. J. Mol. Sci. 2021, 22(23), 12863; https://doi.org/10.3390/ijms222312863 - 28 Nov 2021

Cited by 8 | Viewed by 2353

Abstract

Reductive radical stress represents the other side of the redox spectrum, less studied but equally important compared to oxidative stress. The reactivity of hydrogen atoms (H^•) and hydrated electrons (e^–_aq) connected with peptides/proteins is summarized, focusing on the chemical transformations of methionine (Met) and cystine (CysS–SCys) residues into α-aminobutyric acid and alanine, respectively. Chemical and mechanistic aspects of desulfurization processes with formation of diffusible sulfur-centered radicals, such as methanethiyl (CH₃S^•) and sulfhydryl (HS^•) radicals, are discussed. These findings are further applied to biomimetic radical chemistry, modeling the occurrence of tandem protein–lipid damages in proteo-liposomes and demonstrating that generation of sulfur-centered radicals from a variety of proteins is coupled with the cis–trans isomerization of unsaturated lipids in membranes. Recent applications to pharmaceutical and pharmacological contexts are described, evidencing novel perspectives in the stability of formulations and mode of action of drugs, respectively. Full article

(This article belongs to the Special Issue Radiation and Photochemical Modifications in Proteins: Mechanistic Aspects and Applications)

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