Monoclonal Antibodies for the Detection of a Specific Cyclic DNA Adduct Derived from ω-6 Polyunsaturated Fatty Acids

Dyba, Marcin; Silva, Brandon Da; Coia, Heidi; Hou, Yanqi; Noguchi, S; Pan, Jason; Berry, Deborah L.; Creswell, Karen; Krzeminski, Jacek; Desai, Dhimant; Amin, Shantu; Yang, David C.H.; Chung, Fung Lung

doi:10.1021/acs.chemrestox.8b00111

Cited by 3 publications

(2 citation statements)

References 35 publications

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“…Hence, the derivative DHHεdA has become a major research target in recent years. Dyba et al described the development of monoclonal antibodies specifically against DHHεdA and proposed their application to detect DHHεdA in human cells [ 53 ]. Additionally noteworthy are the results of the research showing for the first time the elevated DHHεdA levels in almost 81% of liver biopsies from young non-alcoholic steatohepatitis (NASH) patients [ 54 ].…”

Section: The Formation and Removal Of Hnementioning

confidence: 99%

Chemistry and Biochemistry Aspects of the 4-Hydroxy-2,3-trans-nonenal

2022

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4-hydroxy-2,3-trans-nonenal (C9H16O2), also known as 4-hydroxy-2E-nonenal (C9H16O2; HNE) is an α,β-unsaturated hydroxyalkenal. HNE is a major aldehyde, formed in the peroxidation process of ω-6 polyunsaturated fatty acids (ω-6 PUFAs), such as linoleic and arachidonic acid. HNE is not only harmful but also beneficial. In the 1980s, the HNE was regarded as a “toxic product of lipid peroxidation” and the “second toxic messenger of free radicals”. However, already at the beginning of the 21st century, HNE was perceived as a reliable marker of oxidative stress, growth modulating factor and signaling molecule. Many literature data also indicate that an elevated level of HNE in blood plasma and cells of the animal and human body is observed in the course of many diseases, including cancer. On the other hand, it is currently proven that cancer cells divert to apoptosis if they are exposed to supraphysiological levels of HNE in the cancer microenvironment. In this review, we briefly summarize the current knowledge about the biological properties of HNE.

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Section: The Formation and Removal Of Hnementioning

confidence: 99%

Chemistry and Biochemistry Aspects of the 4-Hydroxy-2,3-trans-nonenal

2022

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“…The synthesis of nucleobase-based polymers requires challenging isolation of their monomers. Low solubility in nucleobases or reactive functional groups of nucleosides and especially, of integrated ribose require the development of a multi-step synthesis, including protection and deprotection steps [7][8][9]. Applying enzymes as biocatalysts greatly facilitates these syntheses due to their regioselectivity and specificity [10,11].…”

Section: Introductionmentioning

confidence: 99%

Microwave-Assisted Synthesis of 5′-O-methacryloylcytidine Using the Immobilized Lipase Novozym 435

2022

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Nucleobase building blocks have been demonstrated to be strong candidates when it comes to DNA/RNA-like materials by benefiting from hydrogen bond interactions as physical properties. Modifying at the 5′ position is the simplest way to develop nucleobase-based structures by transesterification using the lipase Novozym 435. Herein, we describe the optimization of the lipase-catalyzed synthesis of the monomer 5′-O-methacryloylcytidine with the assistance of microwave irradiation. Variable reaction parameters, such as enzyme concentration, molar ratio of the substrate, reaction temperature and reaction time, were investigated to find the optimum reaction condition in terms of obtaining the highest yield.

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Overview of Adductomics in Toxicology

Lockridge

2023

Current Protocols

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Adductomics is epidemiology at the molecular level. Untargeted adductomics compares levels of chemical adducts on albumin, hemoglobin, and DNA between healthy and exposed individuals. The goal is to determine a cause-and-effect relationship between chemical exposure and illness. Chemical exposures are not necessarily due to synthetic chemicals but are often due to oxidation products of naturally occurring lipids, for example, 4-hydroxynonenal and acrolein produced by lipid peroxidation of arachidonic and linoleic acids. The preferred method used in adductomics is ultra-high pressure liquid chromatography coupled to with nanoelectrospray tandem mass spectrometry. The mass of the adduct indicates its structure and identifies the chemical. The advantages of molecular epidemiology include information about the many toxicants to which a person is exposed over a period of weeks or months and the relative exposure levels. The disadvantage is the absence of information about the mechanism of toxicity. Untargeted adductomics examines albumin and hemoglobin adducts, which serve as biomarkers of exposure but do not identify the proteins and genes responsible for the toxicity. Targeted adductomics is used when the origin of the toxicity is known. This can be either an adducted protein, such as the butyrylcholinesterase protein modified by nerve agents, or a toxicant, such as acetaminophen. Untargeted adductomics methods have identified potential protein adduct biomarkers of breast cancer, colorectal cancer, childhood leukemia, and lung cancer. Adductomics is a new research area that offers structural insights into chemical exposures and a platform for the discovery of disease biomarkers.

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Monoclonal Antibodies for the Detection of a Specific Cyclic DNA Adduct Derived from ω-6 Polyunsaturated Fatty Acids

Cited by 3 publications

References 35 publications

Chemistry and Biochemistry Aspects of the 4-Hydroxy-2,3-trans-nonenal

Chemistry and Biochemistry Aspects of the 4-Hydroxy-2,3-trans-nonenal

Microwave-Assisted Synthesis of 5′-O-methacryloylcytidine Using the Immobilized Lipase Novozym 435

Overview of Adductomics in Toxicology

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