Radiochemistry for Preclinical Imaging Studies
George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos in Handbook of Small Animal Imaging, 2018
Unfortunately, it will be not possible to give here a full list of all important examples for radiolabeling small molecules with carbon-11. Instead, we refer the interested reader to additional articles that report on the use of [11C]iodomethane as starting material for [11C]azidomethane in rapid click chemistry (Schirrmacher et al. 2008) and for Stille cross-coupling chemistry (Samuelsson and Långstr϶m 2003). There are also a number of noteworthy publications on using [11C]carbon monoxide in catalyzed carbonylation reactions (Kihlberg 2002; Kealey et al. 2009; Kealey et al. 2011). There has been much interest in microfluidic devices as tools in the synthesis of carbon-11 labeled tracers (Wang et al. 2010; Kealey et al. 2011). Further comprehensive examples for pre-clinical 11C radiochemistry can be gathered from the review by Allard et al. (2008).
Herbal Product Development and Characteristics
Anil K. Sharma, Raj K. Keservani, Surya Prakash Gautam in Herbal Product Development, 2020
The mode of action of the BACs present in the extracts and in essential oils is the same as the synthetic antioxidants, commonly used in foods, such as BHA, BHT, and TBHQ. They act as free-radical scavengers, blocking free radicals by donating a hydrogen atom (Embuscado, 2015; Tongnuanchan and Bejakul, 2014). As with clinical properties, phenolic compounds are the antioxidants and effective free-radical scavengers, able to impede initiation and cascade of lipid oxidation (Hyldgaard et al., 2012). They are primary antioxidants that act in three steps against lipid oxidation: initiation, propagation, and termination. Their capacity to donate an electron to the free radical prevents the oxidation of other compounds (Yanishlieva-Maslarova, 2001). They react with free (lipid) radicals leading to nonradical species and the inactivation of peroxyl radicals, therefore inhibiting the cascade reactions leading to termination (Jayasena and Jo, 2014). Similar mechanism of action is characteristic for protein oxidation where phenolic compounds avoid protein carbonylation by joining with the proteins (Siebert et al., 1996).
Measuring Oxidative Damage and Redox Signalling
James N. Cobley, Gareth W. Davison in Oxidative Eustress in Exercise Physiology, 2022
Using omics workflows to measure exercise-induced oxidative damage is rate-limited by the time, expertise, and resources required. To expand current non-omic approaches to measure oxidative damage, we propose targeted immunological analysis. For example, manganese superoxide dismutase (MnSOD) activity is inhibited by tyrosine 34 (Y34) nitration to 3-nitrotyrosine (3-NT). Y34 nitration impairs catalysis by disrupting the hydrogen bond network required to protonate manganese bound superoxide (Abreu and Cabelli, 2010). MnSOD immunocapture followed by 3-NT blotting can assess a functionally annotated oxidative damage biomarker. However, appropriate steps to safeguard faithful immunocapture are required (e.g., covalently immobilising the antibody to a solid support). Additionally, reciprocal immunocapture is useful (e.g., confirming a 3-NT antibody elutes MnSOD). Further, immunoblotting is semi-quantitative. In certain cases, fluorophores could be used to achieve quantitative in-gel analysis. For example, a heterobifunctional hydrazine carbonyl reactive warhead with a short polyethylene glycol (PEG) spacer between a fluorescent moiety for quantitative in-gel fluorescent target protein carbonylation analysis.
In silico prediction of post-translational modifications in therapeutic antibodies
Published in mAbs, 2022
Metal ions can catalyze oxidative carbonylation of arginine, Lys, proline (Pro), and threonine residues. Transition metals such as iron and copper can convert oxygen (O2) to superoxide radical anions (O2–·).99 During carbonylation, free radicals attack the side chain and add an amine or ketone group. Arginine and Pro are converted to glutamic semialdehyde; Lys is converted to aminoadipic semialdehyde, and threonine is converted to 2-amino-3-ketobutyric acid (Figure 4).100 Exposure to trace metals from stainless steel surfaces and glass vials can cause carbonylation of mAbs during manufacturing and storage.101 Carbonylation of arginine and Lys residues leads to a loss in positive charge, which generates acidic variants. For example, Yang et al. reported increased acidic variants after forced oxidation with ferrous sulfate and hydrogen peroxide.102 Oxidative carbonylation of mAbs can also increase protein aggregation.103
Tucumã (Astrocaryum aculeatum) extract: phytochemical characterization, acute and subacute oral toxicity studies in Wistar rats
Published in Drug and Chemical Toxicology, 2022
Camille Gaube Guex, Gabriela Buzatti Cassanego, Rafaela Castro Dornelles, Rosana Casoti, Ana Martiele Engelmann, Sabrina Somacal, Roberto Marinho Maciel, Thiago Duarte, Warley de Souza Borges, Cínthia Melazzo de Andrade, Tatiana Emanuelli, Cristiane Cademartori Danesi, Euler Esteves Ribeiro, Liliane de Freitas Bauermann
The development of chronic diseases is associated with oxidative stress, which is characterized by an imbalance between the antioxidant system and reactive species production. Malondialdehyde (MDA) is one of the final products generated by lipid peroxidation and is an important biological marker of oxidative damage (Mansour et al. 2008). Furthermore, protein carbonylation can lead to alteration in protein functions, which may result in the etiology or progression of various diseases (Levine 2002). Enzymes like CAT and SOD are part of an enzymatic defense strategy, which is responsible for neutralizing reactive species, therefore preventing oxidative damage. In this study, CETP was shown to decrease MDA levels in the renal tissue of females and increase SOD activity in the hepatic tissue of males, suggesting that the tucumã fruit may play an important role in preventing oxidative damage. These results may be attributed to the phenolic compounds found in the extract, which are known to possess high antioxidant capacity. Therefore, our results indicate that lower doses of tucumã extract are safe and have possible biological activities that may benefit the prevention and/or treatment of disorders.
Progress and pitfalls of using isobaric mass tags for proteome profiling
Published in Expert Review of Proteomics, 2020
Isobaric mass tags have been modified for the more specific analysis of post-translational modifications (PTMs). For example, some particular chemistries have been developed to directly target protein carbonylation, glycan modifications, or cysteine residues. iTRAQ hydrazide (iTRAQH) was used to probe carbonyl groups [41], aminoxyTMT was described for the quantification of carbonyl-containing compounds [42], and iodoTMT labeling was employed for studying cysteine-containing peptides [43,44]. Indirect methods employing a combination of specific peptide enrichment techniques before or after isobaric labeling have been used to study phosphoproteomes [16,31,45,46] and acetylomes [47,48]. An approach called TAILS for terminal amine isotope labeling of substrates [49] uses isobaric mass tags to distinguish the N-termini of proteins from the N-termini of their protease cleavage products [50,51].
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