Proteosynthesis vs. Proteolysis: How to Bias This Antagonism in Favor of Proteosynthesis
Willi Kullmann in Enzymatic Peptide Synthesis, 1987
The formation of a peptide bond represents a condensation process during which two molecules are connected to each other via an amide bond to generate a new molecule. The product yield depends not only upon the equilibrium of this reaction but also upon the initial concentration of the educts. The degree of synthesis, a, i.e., the relative amount of synthesis of an arbitrary dipeptide of the form A-B, from the constituent amino acids A and B (which contribute the α-imino and the α-carbonyl group, respectively, to the prospective amide bond) can be deduced from the law of mass action in the following way; suppose the initial concentrations of the amino acids A and B are [Ao] and [Bo], respectively. Then, under equilibrium conditions the concentration of the product, the dipeptide A-B, becomes α[Ao], while the concentrations of the educts A and B are reduced to [Ao] – α[Ao] and [Bo] – α[Ao], respectively. Hence, the equilibrium relation reads
Proteasome and Protease Inhibitors
Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey in Innovative Leukemia and Lymphoma Therapy, 2019
The proteasome is present in both the cytoplasm and nucleus of cells (24,25). The 26S proteasome is a large intracellular protease (l,500–2,000kDa) that consists of a 20S core catalytic complex and two 19S regulatory subunits (26–28). The 20S proteasome complex is a macromolecule of 700 kDa, made up of four stacked rings. The two outer rings contain seven α-subunits, while the two inner rings consist of seven β-subunits. The β1, 2, and 5 subunits contain the postglutamyl peptidyl hydrolytic-, tryptic-, and chymotryptic-like proteolytic activities of the proteasome, respectively (26,27,29). Together, these three can hydrolyze almost all peptide bonds of proteins, thus forming smaller polypeptide units. When combined with the two 19S regulatory units, the 26S proteasome is formed. This form of the proteasome is the most important mediator of protein degradation.
Finding a Target
Nathan Keighley in Miraculous Medicines and the Chemistry of Drug Design, 2020
The reaction profile in Figure 2.1 illustrates how the energy difference between the substrate and the transition state at the top of the curve, which is the activation energy, is lowered in formation of an enzyme-substrate complex. Less energy is required for the reaction to proceed, so more encounters between the enzyme and the substrate will lead to a successful reaction, hence rate is increased. The mechanism for hydrolysis of a peptide bond explains how the catalytic process operates. The negative charge of the carboxylate pushes electron density onto the electronegative oxygen atom of the water molecule, making it a strong nucleophile. Meanwhile, the electronegative nitrogen atom of a second amino acid residue pulls electron density from the C=O bond, creating a partial positive charge on the carbon, making it very susceptible to nucleophilic attack from the oxygen lone pair of electrons, hence the reaction proceeds quickly.
Emerging peptide therapeutics for the treatment of ovarian cancer
Published in Expert Opinion on Emerging Drugs, 2023
Ana C. Veneziani, Eduardo Gonzalez-Ochoa, Amit M. Oza
Peptides are composed of short sequences of amino acids and are held together by peptide bonds. They are structural segments of proteins and are subdivided into oligopeptides and polypeptides [42]. Therapeutic peptides and proteins bind to cell receptors with high affinity and trigger intracellular effects. They are vital for cellular activity, such as cell growth, energy metabolism, material transport, signal transmission, and immune regulation [43–45]. Most of these peptides and proteins are expressed on the tumor cell surface and are classified as tumor-associated antigens (TAA). Other emerging targets are the cancer-testis antigens (CTA), which are expressed in a wide range of cancer types. In contrast, their expression in normal tissues is restricted to immune privileged sites such as testis and placenta [46]. Some of these peptides and proteins are ideal targets for cancer-specific immunotherapy.
Methyl and methylene vibrations response in amino acids of typical proteins in water solution under high-frequency electromagnetic field
Published in Electromagnetic Biology and Medicine, 2019
Emanuele Calabrò, Salvatore Magazù
In particular, in this study, we focused on the global response of amino-acids residues in proteins to an applied HF-EMF. Indeed, proteins are formed by peptides chains linked to amino acids by amide bonds. Amino acids are carboxylic acids that contain an amine function. Under certain conditions the amine group of one molecule and the carboxyl group of a second can react, forming two amino acids by an amide bond. Amide linkages between amino acids are known as peptide bonds. Despite more than 700 amino acids are present in nature, only 20 amino acids are present in proteins and represent the repeating units that are called amino-acid residues. The variation of molecules and linkages in these subunits represents the cause of the structural and functional diversity of proteins. A residue is the part of an amino acid that makes it different from each other. Some residues are hydrophilic and are often in the proximity of proteins surface, providing high flexibility to the peptide chains. Other residues are hydrophobic and are located inside the protein giving rigidity to the polypeptide chains. Both type of residues are essential for the numerous functions of proteins in living beings. Amino acids are functional in metabolism, nutrition, growth and reproduction of animals and humans (Wu 2009, 2010).
Non-small cell lung cancer tumour antigen, MUC-1 peptide-loaded non-aggregated poly (lactide-co-glycolide) nanoparticles augmented cellular uptake in mouse professional antigen-presenting cells: optimisation and characterisation
Published in Journal of Microencapsulation, 2020
Kiran Jyoti, Sanyog Jain, Om Prakash Katare, Anju Katyal, Ramesh Chandra, Jitender Madan
The solid phase peptide synthesis (SPPS) method (Made et al.2014) was employed to synthesise MUC-1 peptide as per the desired sequence. The principle of SPPS is based on the reversible blocking of the carboxylic acid function of the C-terminal amino acid and amino group of the N-terminal amino acid. In addition, activation of the free carboxylic group of the N-terminal amino acid is necessary to obtain the peptide bond. For SPPS, two major protecting groups for the N-α-amino have been established namely, Boc (tert-butyloxycarbonyl) (Otaka et al.2015) and F-moc (9-fluorenylmethoxycarbonyl) (Otaka et al.2015). The F-moc protecting group strategy was used for the synthesis of MUC-1 peptide. When the synthesis was finished, it was necessary to deprotect the 9-fluorenylmethoxycarbonyl (Fmoc) group at N-terminal first, and then the side chain protection group was deprotected, and the peptide was cleaved off from the resin.
Related Knowledge Centers
- Amide
- Carboxylic Acid
- Isopeptide Bond
- Organic Chemistry
- Peptide
- Protein
- Amino Acid
- Nitrogen
- Carbon
- Side Chain