China
Africa
Explore chapters and articles related to this topic
Formulation of Protein- and Peptide-Based Parenteral Products
Published in Sandeep Nema, John D. Ludwig, Parenteral Medications, 2019
Gaozhong Zhu, Pierre O. Souillac
The racemization reaction is catalyzed by both acid and base. Racemization of peptides and proteins results in the formation of diastereomers. Racemization under basic conditions is hypothesized to proceed by abstraction of the α-proton from an amino acid in a peptide to yield a negatively charged planar carbanion. A proton can then be returned to this optically inactive intermediate, thus producing a mixture of d- and l-enantiomers for the individual amino acid. Since a peptide is composed of multiple chiral centers, the product formed is a diastereomer. Racemization is biologically significant because a peptide composed of d-amino acids is generally metabolized much more slowly than a naturally occurring peptide made only of l-amino acids. For this reason, many new synthetic peptides, both agonists and antagonists, incorporate d-amino acids. A pH dependency for racemization was demonstrated in an aqueous degradation study of a decapeptide, RS-26306 (42), which found that at neutral and alkaline pHs, racemization contributed to more degradation than did deamidation.
Artificial Enzymes
Published in Yubing Xie, The Nanobiotechnology Handbook, 2012
James A. Stapleton, Agustina Rodriguez-Granillo, Vikas Nanda
Nature has elected to use only l-amino acids at the expense of their mirror-image enantiomers, the d-amino acids. In principle, for each natural protein, a corresponding sequence of d-amino acids will fold into a mirror-image protein with activity against mirror-image substrates. d-peptides are resistant to degradation by proteases, making them promising drug candidates. d-amino acids have been computationally modeled (Nanda and DeGrado 2006) and incorporated into l-peptides to improve stability (Rodriguez-Granillo et al. 2011). Full proteins composed entirely of d-amino acids could be very useful for the synthesis of enantiomers and diastereomers (Forster and Church 2007), or as a safety mechanism to prevent escaped synthetic biological systems from interfering with natural life.
Bioactive Peptides (BPs) as Functional Foods: Production Process, Techno-Functional Applications, Health-Promoting Effects, and Safety Issues
Published in Deepak Kumar Verma, Ami R. Patel, Sudhanshu Billoria, Geetanjali Kaushik, Maninder Kaur, Microbial Biotechnology in Food Processing and Health, 2023
Afshin Babazadeh, Majid Nooshkam, Mahnaz Tabibiazar
Thermal processing at high pH values (alkaline conditions) is able to make adjustments in the structure of amino acids including Arg, Lys, Ser, and Thr. In these conditions Arg is prone to decompose to ornithine. One reason for these changes might be attributed to the racemization phenomenon, in which L-amino acids partially racemized into D-amino acids. This phenomenon is highly occurred in amino acids containing strong electron donor activity in their side chain, i.e., Asp, Phe, Glu, Cys, Asn, Ser, and Thr. It was stated that heating processes induced this phenomenon in roasted bovine serum albumin and casein. Furthermore, L-amino acids can be converted to D-amino acids by microorganisms-based enzymes such as transaminases, epimerases, and amino acid oxidases (Friedman, 1999b). Therefore, fermented milk and ripened cheeses which get the benefits of microorganisms are a good source of D-amino acids. Dehydroalanine residues, highly reactive substances, can be generated from phosphoserine, Cys, Ala, and cystine during high temperature (200°C)-neutral pH or normal heat-alkaline pH conditions. Dehydroalanine residues can react with different amino acids such as Cys, Lys, His, and ornithine and is able to change these amino acids to lanthionine, lysinoalanine, histidinoalanine, and ornithoalanine, respectively. It was reported that thermally treated milk products will contain high levels of lysinoalanine amino acid due to the presence of precursors such as cysteine (in whey proteins) and serine phosphate groups (in casein) (Friedman, 1999a). These changes may influence the sensitivity of peptides to the proteolysis, which consequently can change the bioactive sites of the peptides.
Computational studies on non-succinimide-mediated stereoinversion mechanism of aspartic acid residues assisted by phosphate
Published in Molecular Physics, 2018
Tomoki Nakayoshi, Shuichi Fukuyoshi, Ohgi Takahashi, Akifumi Oda
It has been believed that nearly all of the amino acid residues in higher organisms are l-form, but various d-amino acids, mostly aspartate (Asp) residues, have been recently found in higher organisms [1–5]. Proteins have unique three-dimensional (3D) structures and their conformations highly depend on the amino acid sequences. When amino acid residues are isomerised, the activity of proteins can decrease dramatically with protein conformational change. d-amino acid residues have been detected in crystallin in lens [3], elastin in sun-damaged skin [4], and β-amyloid protein in the brain [5]. The d-amino acid residues are more commonly detected in ageing tissues, so it is presumed that an increase of d-amino acid residues causes age-related diseases. Fujii et al. experimentally derived an Arrhenius plot for stereoinversion of the Asp residue in a human αA-crystallin peptide, from which the activation energy was estimated to be 21.4–28.3 kcal mol−1 [6]. l-Asp residues in proteins are thought to undergo non-enzymatic reactions to form l-β-Asp, d-α-Asp, and d-β-Asp residues via a five-membered ring succinimide intermediate (Scheme 1).