Fundamentals of Modern Peptide Synthesis
Mesut Karahan in 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).
Functional Foods
Datta Sourya, Debasis Bagchi in Extreme and Rare Sports, 2019
β alanine is a non-essential amino acid synthesized by the liver. With histidine, it is the building block for carnosine (a muscle pH regulator and excellent antioxidant) and hence helps in maintaining muscle pH (buffering system), thereby lowering muscle fatigue and improving muscle performance (Artioli et al., 2010). β alanine is also recommended with sodium bicarbonate for endurance athletes for better performance (de Salles Painelli et al., 2013). Researchers have supported the use of β alanine to improve training adaptations (increase training ability-tolerance) through high-intensity training (Hill et al., 2007). Some studies suggested that β alanine supplementation would increase muscle carnosine and thus stabilize the intramuscular pH (lowering H+) during intense training and thereby lower or delay muscular fatigue (Harris et al., 2006; Stout et al., 2007). Hoffman and his co-workers (2007) reported that β alanine consumption might allow for higher intense training volume (stimulus) and eventually result in increased LBM and lower fatigue. Smith et al. (2009) concluded that chronic supplementation of β alanine with high-intensity interval training could significantly increase VO2 peak and LBM due to decreased anaerobic ATP production and thereby improve the endurance performance in a double-blind clinical trial.
-Glutamate(2-Oxoglutarate) Aminotransferases
Elling Kvamme in Glutamine and Glutamate in Mammals, 1988
l-Alanine has long been known to be an important gluconeogenic and ureogenic amino acid in the liver68 and the recent findings of Cornell et al.70 certainly are in accord with this fact. In theory, ureogenesis from alanine in the liver could be accomplished either by coupling ALAAT to ASPAT to provide aspartate nitrogen for urea synthesis or by coupling ALAAT with glutamate dehydrogenase to provide ammonia for urea synthesis (Figure 2). The fact that inhibition of ASPAT had little effect on ureogenesis from alanine would suggest that the latter pathway is more important, at least under the somewhat artificial conditions of the in vitro experiments of Cornell et al. However, other workers have provided evidence for the importance of ASPAT in ureogenesis. Smith and Freedland,71 for example, suggest that stimulation of ureogenesis from ammonia and ornithine by pyruvate involves cASPAT whereas stimulation of ureogenesis by lactate primarily involves mASPAT.
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.
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.
Ixazomib: an investigational drug for the treatment of lymphoproliferative disorders
Published in Expert Opinion on Investigational Drugs, 2019
Piotr Smolewski, Dominika Rydygier
Ixazomib (like bortezomib) is a dipeptide boronic acid. It contains a derivative of the amino acid, with the carboxylic acid group replaced by a citrate-protected boronic acid. The remainder of the molecule has been likened to alanine [30]. Ixazomib is a reversible proteasome inhibitor which acts by binding preferentially to the beta 5 subunit of the 20 S proteasome and inhibiting its chymotrypsin-like activity (Figure 1). At higher concentrations, it inhibits the proteolytic beta 1 (caspase-like) and beta 2 (trypsin-like) sites. Inhibition of proteasome prevents the degradation of IkB, resulting in the suppression of NF-kB activation [31]. The drug is taken orally as a prodrug: ixazomib citrate. On exposure to aqueous solutions or plasma, it rapidly hydrolyzes to its biologically active form, free boric acid metabolite-MLN 2238 (Figures 2 and 3) [32].
Related Knowledge Centers
- Amine
- Carboxylic Acid
- Methyl Group
- Protein
- Metabolism
- Amino Acid
- Preferred Iupac Name
- Chemical Polarity
- Aliphatic Compound
- Zwitterion