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Lactic Acid Bacteria Application to Decrease Food Allergies
Published in Marcela Albuquerque Cavalcanti de Albuquerque, Alejandra de Moreno de LeBlanc, Jean Guy LeBlanc, Raquel Bedani, Lactic Acid Bacteria, 2020
Vanessa Biscola, Marcela Albuquerque Cavalcanti de Albuquerque, Tatiana Pacheco Nunes, Antonio Diogo Silva Vieira, Bernadette Dora Gombossy de Melo Franco
The third stage of LAB proteolytic system takes place once the peptides have been carried into the cell. This step involves the action of various intracellular peptidases and aminopeptidases, which further hydrolyze the oligopeptides into small peptides and amino acids. These enzymes present different and partly overlapping specificities. The first enzymes in action at this stage are the intracellular endopeptidases, general aminopeptidases (PepN and PepC), and the X-prolyl dipeptidyl aminopeptidase (PepX). Several endopeptidases were characterized from LAB, the majority belonging to the group of metallopeptidases, but also some cysteine-peptidases and serine peptidases. A thorough description of these enzymes and their functioning can be found in the studies carried out by Kunji et al. 1996, Savijoki et al. 2006, Liu et al. 2010.
Intracellular Peptide Turnover: Properties and Physiological Significance of the Major Peptide Hydrolases of Brain Cytosol
Published in Gerard O’Cuinn, Metabolism of Brain Peptides, 2020
It now appears that these three originally defined activities are directed toward oligopeptide substrates and not proteins. A fourth recently described activity termed “caseinolytic” is likely to be responsible for the initial degradation of proteins. Chemical modification of the complex discriminates peptidase and proteinase activities. Thus N-acetylimidazole, a mild acetylating agent, inhibits the trypsinlike and peptidyl-glutamylpeptide hydrolyzing activities while stimulating the degradation of β-casein21. 3,4-dichloroisocoumarin, a mechanism-based serine proteinase inhibitor, inhibits all three activities while markedly activating the hydrolysis of β-casein22. At present the exact number of distinct catalytic components within the complex is not known and evidence for still other activities has been presented23,24. It is likely that all activities act in concert to efficiently degrade proteins to small peptide products. A mechanism whereby intermediates arising from the degradation of proteins are efficiently channeled between different catalytic centers has been proposed25.
Vasoactive Intestinal Polypeptide (Vip): A Putative Neurotransmitter In The Cardiovascular System
Published in Geoffrey Burnstock, Susan G. Griffith, Nonadrenergic Innervation of Blood Vessels, 2019
On the other hand, not much is known about the enzymatic breakdown of VIP. Generally, most tissues contain proteases and in some experiments, notably membrane receptor binding studies, it is important to include a suitable protease inhibitor for a good outcome. This type of information has suggested the presence of an enzymatic degrading system.106 In pharmacological experiments on isolated tissue, there appears to be no need for peptidase inhibitors.107 The degradation of VIP has been examined in several types of tissue homogenates where an enzyme has been found to have a fairly good specificity for VIP.108 Application of VIP to blood vessels from various regions invariably elicits dilatation, a response that occurs in parallel with activation of adenylate cyclase. The use of VIP fragments to stimulate vascular adenylate cyclase and relaxation has indicated that the complete 1-28 VIP molecule is necessary for maximum response. Furthermore, exogenously applied VIP mimics the effect of nerve stimulation, clearly demonstrating similarities in vasomotor responses. The discovery of agents that may interact with exogenous or synaptically released VIP has, however, proven to be elusive. One of the most important goals in future studies is to reveal the exact role and the relative importance of VIP in nonadrenergic, noncholinergic vasomotor control as compared with other control mechanisms.
The development of peptide-drug conjugates (PDCs) strategies for paclitaxel
Published in Expert Opinion on Drug Delivery, 2022
Longkun Wang, Hongyuan Chen, Fengshan Wang, Xinke Zhang
Nevertheless, the translation of the peptide-paclitaxel conjugates from the bench to the clinics still faces many hurdles, with only ANG1005 entered clinical research. Firstly, the stability of the peptide-paclitaxel conjugates should be strengthened. Proteolytic degradation of peptides by peptidase can reduce their penetration into tumors and affinity with receptors. Moreover, rapid renal clearance decreases blood circulation time and effectiveness of peptide-paclitaxel conjugates. Further structural modifications are needed in order to improve the stability of the conjugates and prolong their half-life. For example, peptide cyclization, application of D-type amino acid, structural modification through macromolecular material, and so on. Subsequently, the stability of the modified products should be verified by relevant experiments.
Metalloproteinases in disease: identification of biomarkers of tissue damage through proteomics
Published in Expert Review of Proteomics, 2018
Cristina Herrera, Teresa Escalante, Alexandra Rucavado, Jay W. Fox, José María Gutiérrez
Proteinases are classified within the families of metallopeptidases, aspartic peptidases, cysteine peptidases, serine peptidases, threonine peptidases, and a group of as yet unclassified peptidases [4]. Metalloproteinases contain a metal ion in the active site, usually zinc, which activates a water molecule that carries out a nucleophilic attack on the scissile peptide bond. A group of metalloproteinases classified within the ‘Met-zincins’ are characterized by the conserved zinc-binding motif HEXXHXXGXX(H/D) and a Met-turn underlying the active site [5] Through a highly complex interplay with cellular and extracellular substrates and inhibitors, zinc-dependent metalloproteinases participate in the genesis and development of many disease conditions.
A proteogenomic approach to target neoantigens in solid tumors
Published in Expert Review of Proteomics, 2020
Ayushi Verma, Ankit Halder, Soumitra Marathe, Rahul Purwar, Sanjeeva Srivastava
The mutated protein undergoes proteasomal degradation and is fragmented into small peptides of 8–11 amino acids. These peptides are again fragmented into tiny peptides by cytosolic peptidases. These fragmented peptides enter the endoplasmic reticulum through a transporter associated with antigen processing (TAP). Endoplasmic Reticulum (ER) also has ER-resident aminopeptidases (ERAP) that convert the peptide fragments into a very small chain of amino acids, and the peptides further combine with the MHC class I molecules [16]. T cells can only recognize the mutated peptides if presented along with the MHC molecules. The MHC–peptide complex is then transported to the Golgi-body, and secretory vesicles transfer the MHC–peptide complex to the cell’s surface. Cytotoxic T cells recognize the mutated peptides with MHC class I and get activated. Upon activation, cytotoxic T cells release perforin, granzymes, and various cytokines to kill the tumor cell, which in turn helps release more neoantigens and induces the antitumor immune response (Figure 3). Hence, cancer with a higher mutational burden will have higher neoantigens to present and induce the immune response in a better way. Melanoma and small cell lung cancer are among the cancers with a high mutational load. Shelly et al. have identified neoantigens in melanoma and reported the immune response to identified neoantigens [17]. Similarly, Anagnostou et al. have identified the neoantigens recognized by T cells [18]. Likewise, many studies have identified the neoantigens in solid cancers and reported the immune response. Table 2 summarizes the studies which have identified neoantigens using genomic and proteogenomic approaches.