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Pharmaceutics
Special Issues
Targeted Proteolytic Enzymes as Biomedicals and Biopharmaceutics
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Targeted Proteolytic Enzymes as Biomedicals and Biopharmaceutics

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Biologics and Biosimilars".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 15439

Special Issue Editors

Dr. Alexander A. Osmolovskiy

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Guest Editor
Microbiology Department, Lomonosov Moscow State University, Moscow 119991, Russia
Interests: fungal proteases; aspergillus; thrombolysis; fibrinolytic enzymes; limited proteolysis; activators of human plasma proteins; hemostatically active enzymes
Prof. Dr. Alexander V. Kurakov

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Guest Editor
Department of Mycology and Algology, Lomonosov Moscow State University, Moscow 119991, Russia
Interests: mycology; algology

Special Issue Information

Dear Colleagues,

Most available drugs for the treatment and timely prevention of thromboembolic complications have insufficient specificity of action and high cost, and their use in the treatment of these diseases is associated with the risk of side effects. Therefore, the actual problem of modern biopharmacy and biotechnology is to find and develop new methods for producing drugs, in particular, based on proteolytic enzymes of different living organisms.

Huge interest for practical medicine have proteinases with high fibrinolytic activity and the ability to activate some of the hemostatic system proteins by their limited proteolysis. Recent studies showed that plants, animals and microorganisms, especially microscopic fungi are able to secrete proteases, highly cleaving fibrinogen and fibrin and activating protein C, plasminogen, prekallikrein and factor X - core proteins of the hemostatic system, changing the content of which in the blood stream leads to various diseases. Such enzymes are highly specific to these target proteins and may prove to be very promising for the development of drugs and diagnostic products.

Dr. Alexander A. Osmolovskiy
Prof. Dr. Alexander V. Kurakov
Guest Editors

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Keywords

  • thrombolytics
  • anticoagulants
  • targeted proteases
  • fungal proteases
  • mycobiotechnology
  • pharmaceutical biotechnology
  • collagenases
  • elastases
  • keratinases for medical purporses
  • bacterial biofilm proteins hydrolysis

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Published Papers (3 papers)

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9 pages, 234 KiB  
Article
Acute Toxicity, Immunotoxicity and Allergenicity of Protease Complex Obtained from Micromycete Sarocladium strictum
by Svetlana Alipkina, Elena Kornienko, Denis Nalobin and Alexander Osmolovskiy
Pharmaceutics 2021, 13(10), 1660; https://doi.org/10.3390/pharmaceutics13101660 - 11 Oct 2021
Viewed by 1410
Abstract
The different effects on animals of the thrombolytic protease complex of the new producer S. strictum 203 were studied. The tests of acute toxicity, immunotoxicity and allergenicity should conclude that the studied proteolytic complex is safe for medical usage. For the intravenous and [...] Read more.
The different effects on animals of the thrombolytic protease complex of the new producer S. strictum 203 were studied. The tests of acute toxicity, immunotoxicity and allergenicity should conclude that the studied proteolytic complex is safe for medical usage. For the intravenous and the intraperitoneal routes of administration, the maximum tolerated dose and the median lethal dose were not determined. Full article
(This article belongs to the Special Issue Targeted Proteolytic Enzymes as Biomedicals and Biopharmaceutics)

Review

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32 pages, 1178 KiB  
Review
Microbial Fibrinolytic Enzymes as Anti-Thrombotics: Production, Characterisation and Prodigious Biopharmaceutical Applications
by Chhavi Sharma, Alexander Osmolovskiy and Rajni Singh
Pharmaceutics 2021, 13(11), 1880; https://doi.org/10.3390/pharmaceutics13111880 - 5 Nov 2021
Cited by 38 | Viewed by 7357
Abstract
Cardiac disorders such as acute myocardial infarction, embolism and stroke are primarily attributed to excessive fibrin accumulation in the blood vessels, usually consequential in thrombosis. Numerous methodologies including the use of anti-coagulants, anti-platelet drugs, surgical operations and fibrinolytic enzymes are employed for the [...] Read more.
Cardiac disorders such as acute myocardial infarction, embolism and stroke are primarily attributed to excessive fibrin accumulation in the blood vessels, usually consequential in thrombosis. Numerous methodologies including the use of anti-coagulants, anti-platelet drugs, surgical operations and fibrinolytic enzymes are employed for the dissolution of fibrin clots and hence ameliorate thrombosis. Microbial fibrinolytic enzymes have attracted much more attention in the management of cardiovascular disorders than typical anti-thrombotic strategies because of the undesirable after-effects and high expense of the latter. Fibrinolytic enzymes such as plasminogen activators and plasmin-like proteins hydrolyse thrombi with high efficacy with no significant after-effects and can be cost effectively produced on a large scale with a short generation time. However, the hunt for novel fibrinolytic enzymes necessitates complex purification stages, physiochemical and structural-functional attributes, which provide an insight into their mechanism of action. Besides, strain improvement and molecular technologies such as cloning, overexpression and the construction of genetically modified strains for the enhanced production of fibrinolytic enzymes significantly improve their thrombolytic potential. In addition, the unconventional applicability of some fibrinolytic enzymes paves their way for protein hydrolysis in addition to fibrin/thrombi, blood pressure regulation, anti-microbials, detergent additives for blood stain removal, preventing dental caries, anti-inflammatory and mucolytic expectorant agents. Therefore, this review article encompasses the production, biochemical/structure-function properties, thrombolytic potential and other surplus applications of microbial fibrinolytic enzymes. Full article
(This article belongs to the Special Issue Targeted Proteolytic Enzymes as Biomedicals and Biopharmaceutics)
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22 pages, 910 KiB  
Review
Effective Degradation of Gluten and Its Fragments by Gluten-Specific Peptidases: A Review on Application for the Treatment of Patients with Gluten Sensitivity
by Yakov E. Dunaevsky, Valeriia F. Tereshchenkova, Mikhail A. Belozersky, Irina Y. Filippova, Brenda Oppert and Elena N. Elpidina
Pharmaceutics 2021, 13(10), 1603; https://doi.org/10.3390/pharmaceutics13101603 - 2 Oct 2021
Cited by 24 | Viewed by 6057
Abstract
To date, there is no effective treatment for celiac disease (CD, gluten enteropathy), an autoimmune disease caused by gluten-containing food. Celiac patients are supported by a strict gluten-free diet (GFD). However, in some cases GFD does not negate gluten-induced symptoms. Many patients with [...] Read more.
To date, there is no effective treatment for celiac disease (CD, gluten enteropathy), an autoimmune disease caused by gluten-containing food. Celiac patients are supported by a strict gluten-free diet (GFD). However, in some cases GFD does not negate gluten-induced symptoms. Many patients with CD, despite following such a diet, retain symptoms of active disease due to high sensitivity even to traces of gluten. In addition, strict adherence to GFD reduces the quality of life of patients, as often it is difficult to maintain in a professional or social environment. Various pharmacological treatments are being developed to complement GFD. One promising treatment is enzyme therapy, involving the intake of peptidases with food to digest immunogenic gluten peptides that are resistant to hydrolysis due to a high prevalence of proline and glutamine amino acids. This narrative review considers the features of the main proline/glutamine-rich proteins of cereals and the conditions that cause the symptoms of CD. In addition, we evaluate information about peptidases from various sources that can effectively break down these proteins and their immunogenic peptides, and analyze data on their activity and preliminary clinical trials. Thus far, the data suggest that enzyme therapy alone is not sufficient for the treatment of CD but can be used as a pharmacological supplement to GFD. Full article
(This article belongs to the Special Issue Targeted Proteolytic Enzymes as Biomedicals and Biopharmaceutics)
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