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Antibody-Based Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Selenomab antibodies are engineered monoclonal antibodies developed at the Scripps Research Institute (US) (Figure 7.29). They include one or more translationally incorporated selenocysteine residues. The nucleophilic reactivity of the selenol group of a selenocysteine residue allows highly efficient site-specific conjugation of payloads. Selenocysteine is particularly reactive, allowing fast, single-step, efficient reactions under near physiological conditions.Diagram showing the production of Selenomab-drug conjugates based on electrophilic reaction of a linker-payload construct with selenocysteine residues.
Ultratrace Minerals
Published in Luke R. Bucci, Nutrition Applied to Injury Rehabilitation and Sports Medicine, 2020
Selenium is found in two basic forms — inorganic and organic. Inorganic selenium is encountered as water-soluble selenites () and selenates () found in water supplies.1054 Organic selenium is found as selenomethionine and selenocysteine in plant and animal foods. Selenomethionine is the major organic form of selenium in the diet. Selenomethionine is the major storage form of selenium in the body and is converted to selenocysteine in a highly regulated manner for inclusion into GPx enzymes. Selenocysteine can also be produced from inorganic sources. At present, supplemental forms of selenium include sodium selenite, sodium selenate, selenomethionine, and selenium-enriched yeast.
The Modification of Cysteine
Published in Roger L. Lundblad, Chemical Reagents for Protein Modification, 2020
N-Ethylmaleimide reacts with sulfhydryl groups (Figure 13) in proteins with considerable specificity.33-35 The effect of pH on the reaction of free cysteine and N-ethylmaleimide is shown in Figure 14. These determinations were performed in the pH range of 3 to 5 and these investigators estimated that a rate constant of 1.53 × 103M−1 s−1 would be obtained at pH 7.0. This reaction can be followed spectrophotometrically by the decrease in absorbance at 300 nm, the absorbance maximum of N-ethylmaleimide. The extinction coefficient of N-ethylmaleimide is 620 M−1 cm−1 at 302 nm.33 This reaction product yields S-succinyl cysteine on acid hydrolysis. Although the reagent is reasonably specific for cysteine, reaction with other nucleophiles must be considered.36 The use of reaction with N-ethylmaleimide in the identification of selenocysteine has been proposed.37 A “diagonal” procedure for the isolation of cysteine-containing peptides modified with N-ethylmaleimide has been reported (Figure 15).38 This procedure is based on the hydrolysis of the reaction product of cysteine and N-ethylmaleimide to cysteine-S-N-ethyl succinamic acid generating a new negative charge.
Gut associated metabolites and their roles in Clostridioides difficile pathogenesis
Published in Gut Microbes, 2022
Andrea Martinez Aguirre, Joseph A. Sorg
Selenium is an essential component of the proline and glycine reductases. Selenium is incorporated into these proteins as selenocysteine. Selenocysteine is generated through a synthesis pathway where the product of the selD gene reacts inorganic phosphate with hydrogen selenide to generate selenophosphate.58,62,63 A selD mutant is unable to incorporate selenium into proteins and this results in a complete loss of the reductive branch of Stickland metabolism. The loss of selenophosphate generation results in a defect in the ability of C. difficile spores to outgrow following germination in peptide-rich media.63,64 Also, the absence of selenophosphate altered C. difficile physiology so that other NAD+ regeneration pathways were expressed.64
Sex-specific relationship between blood selenium levels and platelet count in a large cohort representative of the United States population
Published in Platelets, 2022
Selenium metabolism is complex and yet to be fully explored. In humans, food is the primary source of selenium intake with four molecules (selenocysteine, selenomethionine, selenite, and selenate) accounting for most of the bioavailable selenium in food [3]. Recommended daily intake for adults is between 55 and 70 μg; intake less than 12μg/day is associated with severe selenium deficiency while an intake above 500 μg/day results in selenium toxicity [16]. The absorption of selenium occurs mainly in the lower part of the small intestine and the gut microbiome may play a role in selenium bioavailability [17]. Once absorbed, selenium is rapidly taken up from circulation by tissues with the highest selenium concentrations found in kidneys, liver, spleen, pancreas, and heart. Excess selenium is excreted in the urine. In the tissues, selenium-based two rare amino acids, selenocysteine and selenomethionine, are incorporated into selenoproteins [18].
Cardiovascular protective effect of nano selenium in hypothyroid rats: protection against oxidative stress and cardiac fibrosis
Published in Clinical and Experimental Hypertension, 2022
Seyed Hamidreza Rastegar Moghaddam, Mahmoud Hosseini, Fereshteh Sabzi, Fatemeh Hojjati Fard, Narges Marefati, Farimah Beheshti, Majid Darroudi, Alireza Ebrahimzadeh Bideskan, Akbar Anaeigoudari
Previously, it has been proved that Selenium is present as selenocysteine in some selenoproteins including iodothyronine deiodinases and thioredoxin reductase in the active catalytic sites of these enzymes (39). Moreover, selenoproteins play a central role in enzymatic redox reactions at the cellular level via selenium-selenocysteine, which is indicative of their antioxidant or catalytic capabilities (40). In addition, the thyroxin system consisting of thioredoxin reductase is a main cellular redox system that effectively sets essential cellular processes including protection against oxidative damage (41). The results of current research showed that intraperitoneal injection of Nano Sel in the highest dose significantly increased the serum thyroxine level compared to the hypothyroid groups. Therefore, it is likely that the treatment with Nano Sel by the positive impact on the thyroxin system can inhibit oxidative stress. In agreement with these findings, other studies confirmed that Nano Sel supplementation could attenuate the negative effect of oxidative stress through activating the antioxidant system and assisting the elimination of free radicals (31,42).