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Fundamentals of Modern Peptide Synthesis
Published in Mesut Karahan, Synthetic Peptide Vaccine Models, 2021
The advantage of the enzymatic route is that D- and L-amino acids can be produced optically pure in higher concentrations and with the formation of a very low byproducts (Ikeda 2003). The reaction time is of great importance in the hydrolysis process, and when this time is recorded, a reaction of enzymes (alcalase and neutrase) occurs for about two days (Ramakrishnan et al. 2013). On the other hand, this method is expensive, and the enzymes are unstable (Ikeda 2003). The use of these enzyme-linked pathways is to derive the D- and L-amino acid isoforms from optically more pure and higher concentrations by minimizing the side derivatives (Ikeda 2003). Therefore, techniques have been developed to improve the performance of the process. Many activities have been provided to improve the process, for example, Hsiao et al. (1988) stated that E. coli immobilized with L-phenylalanine with polyazetidine was used to increase the productivity of 63% (w-w). Since L-amino acid production by chemical synthesis does not show a good result, it is used only in the production of some amino acids such as L-alanine and L-aspartic acid (Zhao et al. 2014).
Biochemistry of Buffering Capacity and Ingestion of Buffers In Exercise and Athletic Performance
Published in Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse, The Routledge Handbook on Biochemistry of Exercise, 2020
Bryan Saunders, Guilherme G. Artioli, Eimear Dolan, Rebecca L. Jones, Joseph Matthews, Craig Sale
The longest supplementation study to date showed that 24 weeks of supplementation at 6.4 g·day−1 did not change clinical markers of health in healthy individuals (103). The available evidence indicates that beta-alanine supplementation (within the doses and durations that have been scientifically investigated) is safe (29). The primary side effect experienced is paraesthesia, which has been described as an uncomfortable prickly sensation on the skin. Paraesthesia most likely occurs due to the binding of beta-alanine to the peripheral neuronal receptor MrgprD (66). Although many individuals consider it an unpleasant sensation, there is no evidence to indicate that it is harmful. The occurrence and intensity of paraesthesia are dose-related and closely relate to the time and peak of blood beta-alanine concentration (45). Accordingly, strategies to slow the time or extent of peak blood beta-alanine, such as splitting the desired dose throughout the day (45) or using a slow-release capsule (26), have been reported to effectively reduce the occurrence or intensity of paraesthesia symptoms.
Cellular and Molecular Mechanisms of Ischemic Acute Renal Failure and Repair
Published in Robin S. Goldstein, Mechanisms of Injury in Renal Disease and Toxicity, 2020
Joseph V. Bonventre, Ralph Witzgall
Weinberg and colleagues have found that glycine and alanine can be protective against injury due to increases in cytosolic free [Ca2+], ROS, ATP depletion, and Na+,K+-ATPase inhibition in isolated kidney tubules and epithelial cells in culture (Weinberg, et al., 1987; Weinberg, et al., 1991a; Weinberg, et al., 1991b). Concentrations of glycine of 0.25 to 2.0 mM are effective. Protection of kidney cells afforded by glutathione has been attributed by Weinberg and colleagues to the formation of glycine due to glutathione degradation (Weinberg, et al., 1989, 1990, 1987). Glutathione is rapidly broken down to cysteine, glycine, and glutamate. Of these agents only glycine is protective. With ischemia in vivo it is unlikely that levels of glycine fall below the concentrations found to be protective; however, depletion of glycine which is permeable to cell membranes may be clinically relevant in the transplanted kidney which may become depleted of glycine during storage. The protective effects of alanine appear to be similar to those of glycine (Garza-Quintero, et al., 1990). The mechanism by which glycine and alanine protect the tubular epithelial cell remains unknown (Weinberg, 1991).
Age Drives the Differences in Dietary Supplement Use in Endurance Athletes: A Cross-Sectional Analysis of Cyclists, Runners, and Triathletes
Published in Journal of Dietary Supplements, 2023
Austin J. Graybeal, Andreas Kreutzer, Jada L. Willis, Kamiah Moss, Robyn Braun-Trocchio, Meena Shah
The positive association between age and use of DS in athletes (6) is therefore unsurprising given the belief that some DS may alleviate these decrements. For instance, omega-3 supplementation and using DS to alleviate joint pain are commonly reported in older adults (23), coinciding with evidence supporting that fish oil supplementation reduces osteoarthritis-specific pain in this group (24). OA may also benefit from planned electrolyte supplementation, given that strenuous exercise and compounding age-related declines in kidney function may lead to more severe imbalances (25). For sports-specific DS, studies show that products such as protein supplements and beta-alanine improve endurance exercise in older adults (26). Thus, it appears that OA have distinct dietary needs (27) and more so now, given recent findings showing that masters athletics is becoming increasingly more competitive (28, 29). Moreover, higher training hours in endurance sports are associated with greater use of DS compared to non-endurance sports such as sprinting (30, 31). However, there are few established DS shown to improve endurance performance (6) and the prevalence of DS in most common endurance events is unknown. Additional insight to the use of dietary supplements in older endurance athletes will further develop the knowledge about patterns of use for DS in a sample of competitive endurance athletes. Therefore, the purpose of this study was to investigate the: (a) use of DS, (b) motivation for use of DS, (c) sources of information for DS, and (d) if these differ by age in endurance athletes who were cyclists, runners, or triathletes.
Identification of AL proteins from 10 λ-AL amyloidosis patients by mass spectrometry extracted from abdominal fat and heart tissue
Published in Amyloid, 2023
Julian Baur, Natalie Berghaus, Sarah Schreiner, Ute Hegenbart, Stefan O. Schönland, Sebastian Wiese, Stefanie Huhn, Christian Haupt
In a first step, we determined the amino acid sequence of the precursor LCs of the different patients. From 2 patients (FOR005, FOR006), the protein sequence of the precursor LCs and their corresponding AL proteins had already been determined as part of a study on the cryo-EM structure of the corresponding fibril [28]. The amino acid sequence of the remaining cases was determined mainly by translation of the cDNA sequence obtained from isolated CD138+ plasma cells. In three out of eight cases (FOR101, FOR142, FOR159) the cDNA sequence contained 1 to 2 uncertain base positions leading to two possible amino acids. With the help of additional MS data, the sequences could be confirmed and it was possible to accurately identify the ambiguous amino acids within one of the two possibilities that resulted from the cDNA sequencing. The only exception in this regard was the case FOR159, where amino acid position 133 in the CL could not be accurately identified because this position is not part of the fibril protein and thus MS could not provide information about this position. However, the DNA sequence at this position encodes for either a valine or an alanine. Since an alanine at this position corresponds to GL and there is no evidence of mutations in this region, the alanine was considered to be the corresponding amino acid.
An overview of ProTide technology and its implications to drug discovery
Published in Expert Opinion on Drug Discovery, 2021
Michaela Serpi, Fabrizio Pertusati
Phosphor(n)amidate technology was applied to carbohydrates, a class of very hydrophilic compounds. McGuigan et al reported the conversion of N-acetylglucosamine to a series of O-6 [117], O-3 and O-4 aryloxy phosphoramidate prodrugs [118], evaluated for their potential chondroprotective activity against osteoarthritis. By comparison to the parent drug, some of the analogues showed a significant enhancement in the inhibition of inflammatory cytokine-induced proteoglycan degradation. Specifically, the O-3 and O-4 (L)-proline prodrugs proved to be the most active of the series, and well processed in chondrocytes. Data on human cartilage supported the notion that these novel O-3 and O-4 regioisomers may represent novel promising leads for osteoarthritis treatment. These findings showed that amino acids other than L-alanine, can be effective promoieties in this technology.