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Inherited Differences in Alpha1-Antitrypsin
Published in Stephen D. Litwin, Genetic Determinants of Pulmonary Disease, 2020
The physiologic importance of proteinase inhibitors can best be demonstrated by experiments of nature in which there is a genetically determined absence or very low concentration of a specific inhibitor. Thus, an inherited low concentration of antithrombin III is associated with intravascular thrombosis presumably due to excessive thrombin activity [2], a genetically determined deficiency of a complement esterase inhibitor in serum leads to hereditary angioneurotic edema [3], and alpha1-antitrypsin deficiency is associated with pulmonary emphysema, as is discussed in detail later.
Proteinase Inhibitors: An Overview of their Structure and Possible Function in the Acute Phase
Published in Andrzej Mackiewicz, Irving Kushner, Heinz Baumann, Acute Phase Proteins, 2020
Proteinase inhibitors constitute a major category of proteins whose synthesis is elevated during the acute phase response in mammals. The simplest explanation is that the organism requires increased synthesis of these proteins to gain control of proteinases released by invading pathogens or by the host during its response to injury and infection. Proteinase inhibitors are usually selective for certain proteinases, and the goal of proteinase inhibitor research in this context is to elucidate the specificity of the interactions. Thus has developed the concept that certain proteinases are targeted for inhibition by certain inhibitors.1,2
α1-Antichymotrypsin (α1-ACh)
Published in Masahiko Mori, Histochemistry of the Salivary Glands, 2019
Human αl-ACh is a glycoprotein which specifically inhibits a chymotrypsin-like enzyme,1,2 which α1-proteinase inhibitor (α1-PI) interacts with elastase, chymotrypsin, and trypsin. Proteinase inhibitors in serum and plasma which control proteolysis in cells and tissues, such as antithrombin III (coagulation system), α2-plasmin inhibitor (fibrinolytic system), and Cl-inactivator (complement pathway), have been described. α1ACh and α1-PI inhibit proteolytic activities of Cathepsin G and leukocyte elastase, respectively.
Recent advances in proteolytic stability for peptide, protein, and antibody drug discovery
Published in Expert Opinion on Drug Discovery, 2021
Xianyin Lai, Jason Tang, Mohamed E.H. ElSayed
To overcome the proteolytic degradation, strategies have been taken based on the administration of the peptide, protein, and antibody drugs. For oral delivery, various approaches have been applied to address the proteolytic stability challenge. Formulation approaches such as liposomes provide a technique to physically separate the drugs from enzymes to avoid proteolytic degradation [18]. Altering the local pH at the delivery site by formulation is able to inhibit the resident peptidases since the optimal pH for the enzymes is changed [21]. Directly using proteinase inhibitors to co-formulate with peptides provides localized protection of peptides [22]. To avoid complex formulations and safety concerns about enzyme inhibition, changing amino acids around the cleavage sites provides a solution for increasing peptide intrinsic proteolytic stability to avoid degradation [23]. For subcutaneous, intravenous, and other non-oral drug delivery approaches, modifying the liable amino acids is the only way to improve their proteolytic stability.
Taenia solium proteins: a beautiful kaleidoscope of pro and anti-inflammatory antigens
Published in Expert Review of Proteomics, 2020
The molecular function enrichment analysis had proteins with binding capacity or catalytic capacity, one among them, fatty acid-binding protein was found to be upregulated in VF as compared to ESPs, they are found in sub-tegumental region or gut epithelium and their presence in ESPs comes as shedding of tegument and appears to be a promising vaccine candidate [68]. Both VF and ESPs had abundant of proteins involved in cell communication: Dynein, Actin, Alpha-2-Macroglobulin etc. Presence of proteinase inhibitors like A2M was interesting as it can inactivate a large variety of important proteinases for host immune response like complement system. In an earlier in silico study, 200 open reading frames encoding proteases of all five clans have been reported to be present in T. solium and KEGG annotation analysis of these proteases had found approximately 60% have strong sequence identity with proteins present in KEGG database [15]. We also reported that the 1.6% of parasite genome is for proteases only. Earlier we had reported that 1.8% of this parasite genome is for its kinome [69] and just like proteases these kinases too are essential for its survival. Based on their essentiality in metabolic pathways and parasite biology, T. solium proteins in ESPs appear to be lucrative target for identification of disease biomarker or efficient diagnosis, with a caution that many proteins have orthologous in humans and they mimic host proteins. Targeting such proteins for new drugs may be deleterious to the host, so care must be taken when probing for drug targeting.
Synergistic Effect of Combined Treatment with Longan Flower Extract and 5-Fluorouracil on Colorectal Cancer Cells
Published in Nutrition and Cancer, 2020
Szu-Jung Chen, Yuan-Chiang Chung, Han-Lung Chang, Hsin-Ping Chang, Jui-Ling Chou, Chih-Cheng Lin, Chih-Hsien Chen, Chih-Ping Hsu
Cell culture media, serum, l-glutamine, trypsin and antibiotics were purchased from Gibco Ltd. (Paisley, UK) (16). Proteinase inhibitor cocktail, sodium orthovanadate, sodium fluoride, sodium pyrophosphate, Triton X-100, ammonia persulfate, rhodamine 123, N,N,N′,N′-tetramethylethylenediamine and Tween 20 were obtained from Sigma (St. Louis, MO, USA). A bicinchoninic acid (BCA) protein assay kit was purchased from Pierce (Rockford, IL, USA). Acrylamide was obtained from Bio-Rad (Hercules, CA, USA). Polyvinylidene fluoride (PVDF) membrane (Immobilon-P) was obtained from Millipore (Bedford, MA, USA). Mouse monoclonal antibodies to caspase-3 were obtained from Zymed (San Francisco, CA, USA), and goat polyclonal antibodies to poly [ADP-ribose] polymerase (PARP) and goat anti-rabbit, anti-mouse, and rabbit anti-goat secondary antibodies conjugated with horseradish peroxidase (HRP) were purchased from R&D Systems (Minneapolis, MN, USA). An Annexin V-based apoptosis kit was obtained from Becton Dickinson (Franklin Lakes, NJ, USA). Longan flowers were purchased from the Peasant Association of Dongshan (Tainan, Taiwan) and identified by Dr. Chih-Cheng Lin and Chih-Ping Hsu using the plant database of Taipei Botanical Garden, Taiwan Forestry Research Institute (Council of Agriculture, Executive Yuan of Taiwan) as a reference (http://tpbg.tfri.gov.tw/PlantContent.php/rid=509). The hot-water reflux extract of longan flowers was defined as LFE and produced as previous reports (12, 16).