Relevant bibliographies by topics / Therapeutic enzymes

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  1. Journal articles
  2. Dissertations / Theses
  3. Books
  4. Book chapters
  5. Conference papers
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Academic literature on the topic 'Therapeutic enzymes'

Author: Grafiati
Published: 4 June 2021
Last updated: 15 February 2022

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Journal articles on the topic "Therapeutic enzymes"

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Städler, Brigitte, and Alexander N. Zelikin. "Enzyme prodrug therapies and therapeutic enzymes." Advanced Drug Delivery Reviews 118 (September 2017): 1. http://dx.doi.org/10.1016/j.addr.2017.10.006.

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Bax, Bridget E. "Erythrocytes as Carriers of Therapeutic Enzymes." Pharmaceutics 12, no. 5 (May 8, 2020): 435. http://dx.doi.org/10.3390/pharmaceutics12050435.

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Therapeutic enzymes are administered for the treatment of a wide variety of diseases. They exert their effects through binding with a high affinity and specificity to disease-causing substrates to catalyze their conversion to a non-noxious product, to induce an advantageous physiological change. However, the metabolic and clinical efficacies of parenterally or intramuscularly administered therapeutic enzymes are very often limited by short circulatory half-lives and hypersensitive and immunogenic reactions. Over the past five decades, the erythrocyte carrier has been extensively studied as a strategy for overcoming these limitations and increasing therapeutic efficacy. This review examines the rationale for the different therapeutic strategies that have been applied to erythrocyte-mediated enzyme therapy. These strategies include their application as circulating bioreactors, targeting the monocyte–macrophage system, the coupling of enzymes to the surface of the erythrocyte and the engineering of CD34+ hematopoietic precursor cells for the expression of therapeutic enzymes. An overview of the diverse biomedical applications for which they have been investigated is also provided, including the detoxification of exogenous chemicals, thrombolytic therapy, enzyme replacement therapy for metabolic diseases and antitumor therapy.
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Noten, J. B. G. M., W. M. A. Verhoeven, S. Tuinier, and D. Touw. "Therapeutic drug monitoring." Acta Neuropsychiatrica 11, no. 1 (March 1999): 15–16. http://dx.doi.org/10.1017/s0924270800036309.

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SUMMARYThe cytochrome P450 iso-enzyme system plays a key role in the biotransformation of many drugs, including psychotropics. Its activity is determined by both genetic and environmental factors. The most important iso-enzymes for psychiatry in general are P450 IID6, 3A4 and 1A2. Knowledge about the involvement of these enzymes and biotransformation processes is mandatory because of the individual variability in their metabolic capacity. Regular measurement of plasmaconcentrations of (psycho)pharmacological compounds is therefore essential. In addition, the potential value of pheno- and/or genotyping has to be investigated.
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Wiederschain, G. Ya, and M. Baldry. "Directory of therapeutic enzymes." Biochemistry (Moscow) 71, no. 11 (November 2006): 1289–90. http://dx.doi.org/10.1134/s0006297906110162.

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Alisi, Anna, Sara Tomaselli, Clara Balsano, and Angela Gallo. "Hepatitis C virus therapeutics: Editing enzymes promising therapeutic targets?" Hepatology 54, no. 2 (July 25, 2011): 742. http://dx.doi.org/10.1002/hep.24409.

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Sioud, Mouldy, and Marianne Leirdal. "Therapeutic RNA and DNA enzymes." Biochemical Pharmacology 60, no. 8 (October 2000): 1023–26. http://dx.doi.org/10.1016/s0006-2952(00)00395-6.

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Maximov, V., V. Reukov, and A. A. Vertegel. "Targeted delivery of therapeutic enzymes." Journal of Drug Delivery Science and Technology 19, no. 5 (2009): 311–20. http://dx.doi.org/10.1016/s1773-2247(09)50066-4.

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Kokotos, George. "Lipolytic enzymes as therapeutic targets." European Journal of Lipid Science and Technology 110, no. 12 (December 2008): 1081–83. http://dx.doi.org/10.1002/ejlt.200800249.

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Azmi, Wamik, and Shabnam Chaudhary. "ARTHROBACTER AS BIOFACTORY OF THERAPEUTIC ENZYMES." International Journal of Pharmacy and Pharmaceutical Sciences 10, no. 11 (November 1, 2018): 1. http://dx.doi.org/10.22159/ijpps.2018v10i11.25933.

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Therapeutic enzymes are proteins which can be used to treat rare and deadly diseases. They represent a small but profitable market. Therapeutic enzymes are superior to non-enzymatic drugs owing to their high specificity toward the target and also their ability to multiple substrate conversion. They are essential for speeding up all the metabolic processes and many a life-supporting chemical inter-conversions. Actinomycetes including Arthrobacter form an enormous reservoir of secondary metabolites and enzymes. The characterization of L-asparaginase, β-glucosidase, urate oxidase, methionine γ-lyase, acetyl cholinesterase, and arginase activities from actinomycetes Arthrobacter clearly demonstrate the potential of Arthrobacter as potent producer of therapeutic enzymes. These metabolic enzymes can be used either separately or in combination with other therapies for the treatment of several diseases such as leukemia, gout, asthma, and neurological disorders. The objective of this review is to compile the information on the application of therapeutic enzymes produced by Arthrobacter and their future prospects as drugs.
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Kaplan, Jeffrey B. "Therapeutic Potential of Biofilm-Dispersing Enzymes." International Journal of Artificial Organs 32, no. 9 (September 2009): 545–54. http://dx.doi.org/10.1177/039139880903200903.

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Surface-attached colonies of bacteria known as biofilms play a major role in the pathogenesis of medical device infections. Biofilm colonies are notorious for their resistance to antibiotics and host defenses, which makes most device infections difficult or impossible to eradicate. Bacterial cells in a biofilm are held together by an extracellular polymeric matrix that is synthesized by the bacteria themselves. Enzymes that degrade biofilm matrix polymers have been shown to inhibit bio film formation, detach established bio film colonies, and render biofilm cells sensitive to killing by antimicrobial agents. This review discusses the potential use of biofilm matrix-degrading enzymes as anti-biofilm agents for the treatment and prevention of device infections. Two enzymes, deoxyribonuclease I and the glycoside hydrolase dispersin B, will be reviewed in detail. In vitro and in vivo studies demonstrating the anti-biofilm activities of these two enzymes will be summarized, and the therapeutic potential and possible drawbacks of using these enzymes as clinical agents will be discussed.
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Dissertations / Theses on the topic "Therapeutic enzymes"

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Gordon, Nathaniel Charles. "Protease engineering for therapeutic applications." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648185.

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Vigne, Aurélie. "Microfluidic tools for the engineering of enzymes of therapeutic interest." Thesis, Bordeaux, 2018. http://www.theses.fr/2018BORD0391/document.

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Cette thèse concerne le développement d’outils microfluidique pour l’ingénierie d’enzymes d’intérêt thérapeutique. La microfluidique à base de gouttelettes présente un énorme potentiel dans le domaine de la biologie quantitative. Nous développons des outils microfluidiques pour l’évolution dirigée de l’enzyme L-asparaginase, enzyme utilisée comme traitement de laleucémie lymphoblastique aiguë. Ce traitement est basée sur une enzyme d’origine bactérienne,ce qui conduit à déclencher des réactions immunitaires qui se traduit par l’interruption du traitement, souvent fatale pour le patient. Cependant, une version humaine de l’enzyme L-asparaginase, qui est moins immunogénique, n’est à l’heure actuelle pas suffisamment active pour être utilisée. L’objectif principal de cette thèse est d’alors d’analyser et de cribler des banques de mutants d’enzymes en utilisant des méthodes classiques de mutagenèse et d’analyser chaque mutant individuellement par le biais de la microfluidique. Pour cela, plusieurs systèmes microfluidiques ont été développés et optimisés afin de répondre à différents critères de sélection pour l’analyse et la sélection de l’enzyme L-asparaginase. La version bactérienne a servi de contrôle positif pour l’optimisation des systèmes microfluidiques afin de pouvoir analyser et de cribler des banques de mutants de la version humaine de l’enzyme L-asparaginase
This thesis deals with the development of microfluidic tools for the engineering ofenzymes of therapeutic interest. Droplet microfluidics has enormous potential in the field ofquantitative biology. We are developing microfluidic tools based on the directed evolutionof the enzyme L-asparaginase, an enzyme used to treat acute lymphoblastic leukemia. Thistreatment is based on an enzyme of bacterial origin, which leads to immune reactions thatresult in the interruption of treatment, often fatal for the patient. However, a human version ofthe enzyme L-asparaginase, which is less immunogenic, is currently not sufficiently active to beused. The main objective of this thesis is to analyze and screen enzyme mutant libraries usingstandard mutagenesis methods and to analyze each mutant individually through microfluidics.For this, several microfluidic systems have been developed and optimized for different selectioncriteria for the analysis and selection of the enzyme L-asparaginase. The bacterial versionserving as a positive control for the optimization of microfluidic workflows to analyze andscreen mutant libraries of the human version of the enzyme L-asparaginase
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Lovering, Andrew Lee. "X-ray crystallographic studies of therapeutic enzymes : nitroreductase and AKR1C3." Thesis, University of Birmingham, 2003. http://etheses.bham.ac.uk//id/eprint/3588/.

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The \(Escherichia\) \(coli\) enzyme nitroreductase has been proposed as a candidate for the Gene-Directed Enzyme Prodrug Therapy approach in treating cancer. Structural studies on the enzyme were instigated in a first step towards improving enzyme activity. The enzyme was crystallized with the substrate analogue, nicotinic acid, and the structures of three crystal forms obtained. The fold has a mixed a/P structure, with a molecule of nicotinic acid bound next to the FMN cofactor. Several active site residues were identified as candidates for mutation. This procedure produced many mutant enzymes with increased catalytic activity. One double and four single mutants were chosen from these and crystal structures determined. The resulting information from this, and the establishment of a proof of principle, provides the basis for iterative cycles of enzyme improvement. The human hydroxysteroid dehydrogenase AKR1C3 has been proposed to play a role in prostaglandin metabolism. Its inhibition by non-steroidal anti-inflammatory drugs may be important in a tumour differentiation strategy. AKR1C3 was crystallized, and the structure solved with bound nucleotide cofactor and several inhibitors, including the drugs indomethacin and flufenamic acid. Having obtained information on drug binding to AKR1C3, selective inhibitors can be designed, avoiding inhibition of "housekeeping" enzymes such as cyclo-oxygenases.
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Guiney, Daniel. "Design and synthesis of inhibitors of enzymes in the folate biosynthesis pathway." Thesis, University of Strathclyde, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.273387.

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Hart, R. J. "Developing protein conjugation techniques to enhance cell delivery of therapeutic enzymes." Thesis, University of Sheffield, 2017. http://etheses.whiterose.ac.uk/18996/.

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The focus of disease research often surrounds therapeutic pathway identification and the subsequent investigation of proteins or compounds that potentially interfere with disease mechanisms. However, finding targets and effective therapeutic domains often overshadows another important aspect of drug delivery and efficacy; the method of domain conjugation. Unfortunately the combination of good therapeutic components and good therapeutic design can often be amiss, with differing skills and groups needed to marry the two together. In recognition of this, there are new techniques emerging that aim to not only address old problems of stable conjugation, but incorporating new knowledge of drug design. This research takes a reverse approach to drug design in order to better comprehend requirements which are often an afterthought; first looking at conjugation technique and then how it can best be exploited. Thereby, exploring how different conjugation methods can be used to complement existing therapeutic and internalisation strategies. Here, two methods of conjugation were investigated through attachment of bacterial toxin domains derived from botulinum A and diphtheria, with the intention of targeting neuroblastoma cells using a variety of specific and non-specific pathways. Both conjugation techniques proved to be stable in vitro and capable of binding a variety of domains consistently. The data here also emphasized the importance of endosomal escape proteins to increase the translocation of catalytic domains into the cytosol. It was demonstrated that the conjugates formed were able to facilitate the binding between targeting and catalytic domains, enabling specific neuroblastoma internalisation. Moreover, that three domains were able to conjugate together using a linking method and could form a co-operative triple-functioning complex.
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Maheshwari, Sweta. "Caractérisation biochimique et cellulaire des enzymes clés du métabolisme des phospholipides chez Plasmodium falciparum." Thesis, Montpellier 2, 2012. http://www.theses.fr/2012MON20004.

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Le développement du parasite Plasmodium falciparum, responsable du paludisme, nécessite la synthèse de phospholipides et plus particulièrement de phosphatidylcholine (PC) et phosphaditylethanolamine (PE) qui représentent environ 85% de la totalité des phospholidipes du parasite. Leur synthèse s'effectue principalement par les voies métaboliques de novo, voies de Kennedy, en trois étapes enzymatiques. Les enzymes CTP: phosphoethanolamine cytidylyltransferase (ECT) et CTP: phosphocholine cytidylyltransferase (CCT) catalysent les étapes limitantes des deux voies de biosynthèse de la PE et de la PC, respectivement. Ces deux enzymes sont essentielles à la survie du parasite murin, P. berghei et représentent ainsi des cibles thérapeutiques potentielles. La PfCCT est constituée de deux domaines cytidylyltranférases (CT) répétés alors que l'enzyme homologue chez l'homme est composée d'un seul domaine. En revanche, pour la ECT, la présence de deux domaines CT est retrouvée chez toutes les espèces mais les analyses de séquences et de structures ont montré que des résidus importants du site catalytique liant le substrat n'étaient pas conservés dans le domaine CT C-terminal de la PfECT. Ce travail a eu pour but de déterminer les propriétés enzymatiques et les caractéristiques cellulaires de la PfECT et de la PfCCT. Les paramètres cinétiques de ces enzymes ont été quantifiés in vitro à l'aide protéines recombinantes ainsi que sur les enzymes endogènes à l'aide d'extraits parasitaires. Grâce à l'utilisation de protéines recombinantes ponctuellement mutées, nous avons montré que seul le domaine CT N-terminal de la PfECT est catalytiquement actif. Chez P. falciparum, la PfECT et la PfCCT sont exprimées tout au long du cycle intra-érythrocytaire du parasite. La PfECT est présente dans la fraction soluble du parasite alors que la PfCCT apparait aussi bien dans la fraction soluble qu'insoluble. Des expériences d'immunofluorescence ont montré que la PfECT est cytosolique. L'ensemble des résultats présentés apportent un éclairage important sur les fonctions et les propriétés de ces deux cibles potentielles et constituent les premières étapes indispensables à l'élaboration d'une approche thérapeutique
Phospholipids are essential for the growth and development of Plasmodium falciparum malaria parasite. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are its major structural phospholipids. This study focused on CTP: phosphoethanolamine cytidylyltransferase (ECT) and CTP: phosphocholine cytidylyltransferase (CCT) that catalyzes the rate-limiting steps of the de novo Kennedy pathways for PE and PC biosynthesis respectively. Both ECT and CCT are essential in the rodent malaria parasite P. berghei and constitute potential chemotherapeutic targets to fight against malaria. PfCCT consists of two very similar cytidylyltransferase (CT) domains whereas the human enzyme consists of only one CT domain. The presence of two CT domains in ECT seems to be widespread in all the organisms. Sequence and structural analysis showed that the C-terminal CT domain of ECT lacks key residues in the substrate binding motif. This study aimed at unravelling the enzymatic properties and cellular characteristics of PfECT and PfCCT enzymes. In addition, these studies addressed the key question if C-terminal CT domain of PfECT is catalytically active. Kinetic parameters of the enzymes were evaluated in vitro on native proteins as well as on recombinant proteins, the latter being produced in bacterial system. Cellular characterisation studies using polyclonal antisera showed that PfECT and PfCCT are expressed throughout the intra-erythrocytic life cycle of the parasite. PfECT is found mainly in soluble form in the parasite while PfCCT is present in soluble as well as insoluble forms in the parasite. Furthermore, immunofluorescence studies for PfECT revealed that it is mainly cytosolic. To assess the contribution of each CT domain to overall PfECT enzyme activity, recombinant PfECT mutants were generated by site-directed mutagenesis. Kinetic studies on these mutants indicated that the N-terminal CT domain was the only active domain of PfECT. Collectively, these results bring new insights into the kinetic and cellular properties of the enzymes and will pave the way in developing a future pharmacological approach
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Mao, Wei. "Etude biochimique et sélection d'inhibiteurs spécifiques d'une cible thérapeutique leishmanienne : la GDP-Mannose-Pyrophosphorylase." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS481.

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Les leishmanioses sont des maladies tropicales négligées provoquées par un protozoaire parasite du genre Leishmania, et transmises par un insecte vecteur, le phlébotome. Les leishmanioses menacent 310 millions de personnes dans 98 pays à travers le monde. Les traitements antileishmaniens actuels sont limités et présentent des problèmes majeurs de toxicité et d'émergence de chimiorésistance. Dans ce contexte, il est nécessaire de développer de nouveaux agents antileishmaniens spécifiquement dirigés contre une cible thérapeutique chez le parasite. La GDP-Mannose Pyrophosphorylase (GDP-MP) est une cible thérapeutique essentielle à la survie du parasite à la fois in vitro et in vivo. Plusieurs différences ont été identifiées dans le site actif de GDP-MPs leishmaniennes par rapport à l'enzyme humaine, montrant ainsi l'intérêt de cette cible thérapeutique dans le développement de nouveaux traitements contre la leishmaniose. La GDP-MP catalyse la synthèse du GDP-mannose, la forme activée du mannose, brique moléculaire importante dans les processus de glycosylation et la synthèse de glycoconjugués essentiels à la reconnaissance hôte-parasite. Ce travail de thèse a consisté à produire et purifier les GDP-MPs de 3 espèces de parasites (Leishmania infantum, Leishmania donovani et Leishmania mexicana) ainsi que l'homologue humaine dans le but de comparer leurs propriétés enzymatiques. A partir d'inhibiteurs potentiels conçus et synthétisés sur la base de modèles moléculaires de GDP-MPs leishmaniennes et humaine, 100 composés ont été évalués sur les enzymes purifiées et sur les parasites in vitro. Cette analyse nous a permis de sélectionner des composés spécifiquement dirigés contre la cible du parasite et présentant une activité antileishmanienne. Nous avons également initié une étude de l'expression et de la localisation de la GDP-MP après traitement par les composés les plus intéressants. Ces composés pourront par la suite être utilisés comme outils pharmacologiques pour le développement de nouveaux agents antileishmaniens spécifiques
Leishmaniases are Neglected Tropical Disease (NTD)caused by a protozoan parasite of the genus Leishmania and transmitted by an insect vector, the phlebotomine sandfly. Leishmaniases threaten 310 millions people in 98 countries around the world. Current antileishmanial treatments are limited and present major issues of toxicity and drug resistance emergence. In this context, it is necessary to develop new specific antileishmanial drugs specifically directed against a therapeutic target in the parasite.The GDP-Mannose Pyrophosphorylase (GDP-MP) is a therapeutic target which has been described to be essential for parasite survival both in vitro and in vivo. Several differences have been identified in the active site of leishmanial GDP-MPs compared to the human counterpart, showing the prominence of this therapeutic target in the development of new treatments against leishmaniasis. The GDP-MP catalyzes the synthesis of GDP-Mannose,the activated form of mannose, an important molecular constituent of the glycosylation processes involved in the biosynthesis of glycoconjugates which are essential for host-parasite recognition. My thesis work consisted in the production and purification of GDP-MPs from 3 Leishmania species (Leishmania donovani,Leishmania infantum and Leishmania mexicana)and from humanin order to compare their enzymatic properties. From potential inhibitors designed and synthesized on the basis of leishmanial and human GDP-MP molecular models, 100 compounds were evaluated on purified enzymes and on parasites in vitro. These analyses allowed us to select some compounds which are specifically directed against the parasite target and presenting antileishmanial activities. We have also initiated a study of expression and localization of GDP-MP after treatment with the most potent compounds. These compounds will be used as pharmacological tools for the development of new specific antileishmanial drugs
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Mendieta, Martínez Laura. "Protease inhibitors as therapeutic agents." Doctoral thesis, Universitat de Barcelona, 2014. http://hdl.handle.net/10803/279388.

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Proteases are involved in a high number of diseases, and thus, are relevant targets. For that reason our main goal was the discovery of protease inhibitors as therapeutic agents. We focused our study in four proteases: dipeptidyl peptidase IV (diabetes mellitus type 2), prolyl oligopeptidase (cognitive disorders) and cathepsins L and B (cancer).For the discovery of inhibitors, three strategies were selected: medicinal plant screening, high throughput screening and the characterization of a combinatorial chemistry library. Once accomplished the DPP IV recombinant expression optimization, the protein was studied by means of nuclear magnetic resonance (NMR) in order to obtain information of its dynamism. Since DPP IV is a large protein, a strategy combining selective labeling and the use of TROSY-HSQC experiments was used. From the 14 methionine residues of the protease, 11 of them were detected in the NMR spectra. Then, a study of the inhibitor effect on the NMR spectra of DPP IV was done. Interestingly, the corresponding spectra of DPP IV / inactivator afforded an extra signal. We believe that it is a consequence of a small structural change that the protease suffers after inhibition. Afterwards, we planned to find DPP IV from botanical sources. First, we selected plants that were already reported to have antidiabetic action. Common antidiabetic plants were chosen, as well as Brazilian plants and others from the Traditional Chinese Medicine. Besides, a library of Mediterranean plants was also selected. After, extraction and testing of DPP IV inhibitory activity was done. From our tailored collection, the plant AP-3 was selected for further analysis. After fractionation and purification, two molecules were found to be DPP IV inhibitors. Kinetic experiments of the best one, AP-3-a, demonstrated that it was inhibiting DPP IV in a parabolic manner. Then, AP-3-a inhibition of DPP IV was analysed by NMR. The extra signal that was observed with competitive inhibitors was not present. We hypothesized that the lack of appearance of this signal is a result of the parabolic inhibition of AP-3-a. Then, we planned the identification of POP inhibitors by HTS. Our strategy was based in the use of libraries containing non-toxic compounds and lead-like properties. The assay we selected was FP, which allowed the identification of protein binders by competition with a fluorophore-labelled probe. First, the peptide probes were validated as useful probes for the FP assay. Then, the HTS was carried out. Over the 4,500 tested compounds, 73 hits were found to be POP binders. Later, 37 hits were selected by means of clustering, docking data and FP results in order to be validated as POP inhibitors. The subset of molecules was evaluated by enzymatic assays. Six compounds presenting the highest POP inhibition ration were selected for further study. Finally, two POP inhibitors have been described. HTS-43 is a competitive POP inhibitor and HTS-75 displays a parabolic behaviour. It was the first time that parabolic inhibition is reported for POP. We believe that the existence of a non-competitive site would help in the understanding of the relationship between POP and mental diseases. Finally, a novel peptidyl aryl vinyl sulfone library was tested for its inhibitory activity against cathepsins L and B. Among all the 20 molecules of the library, a potent covalent irreversible cathepsin L inhibitor has been found, PAVS-20. The progress-curve of the pre-incubation time representation allowed the calculation of its inhibition constants. Furthermore, evaluation of subsite preferences was done by docking analysis. This allowed understanding the experimental differences in inhibition constants obtained for similar compounds. Since cathepsins L and B are targets for cancer, molecules of the PAVS library are promising candidates for the development of new anticancer drugs.
Las proteasas están involucradas en un alto número de enfermedades y por lo tanto, son dianas terapéuticas relevantes. Por este motivo, nuestra principal meta era el descubrimiento de inhibidores de proteasas cómo agentes terapéuticos. Para ello nuestro estudio en cuatro proteasas: la dipeptidil peptidasa IV, la prolil oligopeptidasa y las catepsinas L y B. Para la búsqueda de inhibidores, se seleccionaron tres estrategias: cribado de plantas medicinales, cribado de alto rendimiento y caracterización de una biblioteca proveniente de la química combinatoria. Una vez se llevó a cabo la expresión recombinante de la DPPIV, la proteína se estudió mediante resonancia magnética nuclear (NMR) para obtener información acerca de su dinamismo. Dado que es una proteína grande, se utilizó una estrategia en la que se combinó el marcaje selectivo y el uso de experimentos TROSY-HSQC. Posteriormente, se realizó el estudio de la DPP IV en presencia de sus inhibidores, para observar como estos afectan a la estructura proteica. Después, se realizó la búsqueda de inhibidores de la DPP IV a partir de extractos de plantas medicinales. De nuestra colección, se seleccionó el extracto de la planta AP-3 para un análisis en profundidad. Se detectaron dos inhibidores de la proteasa. El más potente, AP-3-a, se caracterizó cómo un inhibidor parabólico. Después se llevó a cabo el estudio del complejo DPP IV/AP-3-a por NMR. En cuanto a la POP, se realizó la búsqueda de inhibidores mediante cribado de alto rendimiento (HTS). De los 4,500 compuestos testados se obtuvo un total de 73 hits en el ensayo de polarización de la fluorescencia (FP). La validación de estas moléculas mediante docking, clustering y ensayos enzimáticos, permitió identificar seis potentes inhibidores de POP. Uno de ellos, HTS-75, se caracterizó como un inhibidor parabólico. Esta es la primera vez que se describe un inactivador de este tipo para POP. Finalmente, en cuanto a las catepsinas L y B, se cribó una librería de peptidil aril vinil sulfonas. Entre las 20 moléculas testadas se encontró un potente inhibidor irreversible de la catepsina L, el PAVS-20. Además, se realizó un estudio de docking que permitió evaluar las preferencias de los subsitios de las dos proteasas.
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Mirza, Ahmad. "Structural characterization of novel antimicrobial therapeutic targets and crystallographic examination of enzymes involved in xenobiotic metabolism." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=86555.

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Part I. Recently there has been an alarming rise in the number of infections due to pathogenic organisms that are insensitive to our current arsenal of pharmaceuticals, necessitating the identification of new antimicrobial targets. Here, we describe structural studies of two enzymes from the aspartate family of biosynthetic enzymes in order to assess their potential for drug targeting. Our first report details how an unlikely inhibitor with low millimolar binding characteristics, 5-hydroxy-4-oxo-norvaline, can effectively inactivate homoserine dehydrogenase (HSD) through the formation of a tight-binding covalent adduct. This is followed by the structural characterization of the first phenolic-based non-amino acid inhibitor of HSD, which is shown to occupy the substrate binding site and make specific contacts with residues involved in catalysis. Together, these studies lay the foundation for further structure-based drug design of novel inhibitors of HSD. Following this, we report the first structure of the next enzyme in the aspartate pathway, homoserine transacetylase (HTA). As the committal step in microbial methionine biosynthesis, this enzyme is essential to microbial survival. The high-resolution crystal structure identifies HTA as a new member of a larger structural family of enzymes known as the alpha/beta hydrolases. Using the structure as a guide, we propose a rationale for the previously reported ping-pong reaction mechanism for this enzyme. We conclude with a preliminary look into how the natural substrate, homoserine, binds in the active site and some subtle differences between HTAs from different sources.
Part II. Microbes have long been admired for their ability to process virtually any chemical. In Part II of this work we will engage in the structural characterization of two enzymes involved in the microbial degradation of xenobiotic compounds. The first enzyme, cyclohexylamine oxidase (CHAO), is the enabling step in the bacterial metabolism of cyclohexylamine. Preliminary crystallographic analysis of cofactor bound and ternary complexes of CHAO, will be used to highlight differences between this enzyme and its closest human homologue. This information will then be used to direct structure inspired mutagenesis studies in order to better understand the substrate specificity of this enzyme and how it might be altered. Finally, the last enzyme to be discussed in this work will be cyclohexanone monooxygenase (CHMO). Also from the same biodegradation pathway as CHAO this enzyme is responsible for the stereo- and regio- specific conversion of small cyclic ketones into lactones. This reaction, known as the Baeyer-Villiger Oxidation, is of tremendous importance in the pharmaceutical industry as lactones often serve as the building blocks of other larger compounds. Surprisingly, despite many years of research there has never been a published report on the structure of this enzyme. We detail here, for the first time, the crystallographic structure of CHMO in multiple conformations. Together, the various structures of CHAO and CHMO presented will provide insight into how bacteria are able to process xenobiotics and how we might use this information for structure based protein design.
Partie I. Récemment, il y a eu une augmentation alarmante du nombre d'infections causées par des organismes pathogènes qui sont insensibles aux produits pharmaceutiques existants, d'où la nécessité d'identifier de nouvelles cibles antimicrobiennes. Ici, nous décrivons des études structurales de deux enzymes de la famille des enzymes de biosynthèse de l'aspartate afin d'évaluer leur potentiel en tant que cible pharmaceutique. Notre première étude décrit comment un improbable inhibiteur avec une liaison de l'ordre du millimolaire, 5-hydroxy-4-oxo-norvaline, peut inactiver l'homosérine déshydrogénase (HSD) par la formation d'un complexe covalent stable. L'étude est suivie par la caractérisation structurale du premier inhibiteur de l'HSD qui est dérivé du phénol et non d'un acide aminé, et dont nous démontrons qu'il occupe le site de liaison du substrat et forme des contacts spécifiques avec les résidus impliqués dans la catalyse. Mis ensembles, ces études jettent les bases pour la conception de nouveaux adjuvants de l'HSD basée sur la structure. Suite à cela, nous rapportons la première structure de l'enzyme suivante dans la voie métabolique de l'aspartate, l'homosérine transacétylase (HTA). Cette enzyme est essentielle à la survie microbienne, car elle catalyse une réaction déterminante de la biosynthèse microbienne de la méthionine. La structure cristalline à haute résolution identifie l'HTA comme un nouveau membre d'une large famille structurale d'enzymes appelées les alpha/beta hydrolases. En utilisant la structure comme guide, nous proposons une explication pour le mécanisme de réaction ping-pong rapporté antérieurement pour cette enzyme. Nous concluons avec une perspective sur la façon dont le substrat naturel, l'homosérine, lie le site actif, ainsi que sur les différences subtiles qui existent entre les HTA provenant de sources différentes.
Partie II. Les microbes ont depuis longtemps été admirés pour leur capacité à transformer littéralement n'importe quel composé chimique. Dans la deuxième partie de cette thèse, nous entreprenons la caractérisation structurale de deux enzymes impliquées dans la dégradation microbienne des composés xénobiotiques. La première enzyme, la cyclohexylamine oxidase (CHAO), est l'étape déterminante dans le métabolisme bactérien de la cyclohexylamine. L'analyse cristallographique préliminaire de CHAO lié avec un co-facteur ou en complexe ternaire sera utilisée pour souligner les différences entre cette enzyme et son homologue le plus près chez l'humain. Cette information sera ensuite utilisée pour diriger des études de mutagénèse inspirées de la structure afin de mieux comprendre la spécificité de l'enzyme envers son substrat et comment celle-ci pourra être altéré. Enfin, la dernière enzyme dont nous discuterons dans ce travail sera la cyclohexanone monooxygenase (CHMO). Provenant de la même voie métabolique de dégradation que la CHAO, cette enzyme est responsable pour la conversion stéréo- et régio-spécifique de petites cétones cycliques en lactones. Cette réaction, connu sous le nom d'oxydation Baeyer-Villiger, est d'une importance capitale pour l'industrie pharmaceutique car les lactones servent de précurseurs pour la synthèse d'autres composés plus grands. Étonnamment, en dépit de nombreuses années de recherches, il n'y a jamais eu de publication rapportant la structure de cette enzyme. Ici, nous décrivons pour la première fois la structure cristallographique de la CHMO dans des conformations multiples. Ensemble, les structures de CHAO et CHMO présentées ici nous permettront de mieux comprendre comment les bactéries transforment les composés xénobiotiques et comment cette information pourra être utilisé pour l'ingénierie de protéine basée sur la structure. fr
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Chen, Shen-En Trawick Mary Lynn. "Modeling, design, and development of potential inhibitors of [gamma]-glutamylamine cyclotransferase and inhibitors of cruzain as therapeutic agents for Chagas' disease." Waco, Tex. : Baylor University, 2008. http://hdl.handle.net/2104/5189.

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Books on the topic "Therapeutic enzymes"

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Cichoke, Anthony J. Enzymes, nature's energizer. New Canaan, Conn: Keats Pub., 1997.

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Labrou, Nikolaos, ed. Therapeutic Enzymes: Function and Clinical Implications. Singapore: Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-13-7709-9.

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Cichoke, Anthony J. Enzymes the sparks of life. Summertown, Tenn: Books Alive, 2008.

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Lee, Lita. The enzyme cure: How plant enzymes can help you relieve 36 health problems. Tiburon, Calif: Future Medicine Pub., 1998.

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Bickerstaff, Gordon F. Enzymes in industry and medicine. London: E. Arnold, 1987.

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DeFelice, Karen L. Enzymes : go with your gut: More practical guidelines for digestive enzymes. [Johnston, IA]: ThunderSnow Interactive, 2006.

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Cichoke, Anthony J. Enzymes and enzyme therapy: How to jump start your way to lifelong good health. New Canaan, Conn: Keats Pub., 1994.

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Enzymes and enzyme therapy: How to jump-start your way to lifelong good health. 2nd ed. Los Angeles, CA: Keats Publishing, 2000.

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Howell, Edward. Food enzymes for health and longevity. 2nd ed. Twin Lakes, WI: Lotus Press, 1994.

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Howell, Edward. Enzyme nutrition: The food enzyme concept. Wayne, N.J: Avery, 1985.

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Book chapters on the topic "Therapeutic enzymes"

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Nampoothiri, K. Madhavan, Abdulhameed Sabu, and Ashok Pandey. "Therapeutic Enzymes." In Enzyme Technology, 697–707. New York, NY: Springer New York, 2006. http://dx.doi.org/10.1007/978-0-387-35141-4_35.

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Kumar, Swaroop S., and Sabu Abdulhameed. "Therapeutic Enzymes." In Bioresources and Bioprocess in Biotechnology, 45–73. Singapore: Springer Singapore, 2017. http://dx.doi.org/10.1007/978-981-10-4284-3_2.

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Lutz, Stefan, Elsie Williams, and Pravin Muthu. "Engineering Therapeutic Enzymes." In Directed Enzyme Evolution: Advances and Applications, 17–67. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-50413-1_2.

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Torchilin, Vladimir P. "Immobilization of Therapeutic Enzymes." In Progress in Clinical Biochemistry and Medicine, 13–28. Berlin, Heidelberg: Springer Berlin Heidelberg, 1991. http://dx.doi.org/10.1007/978-3-642-75821-8_3.

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Pişkin, A. Kevser. "Therapeutic Potential of Immobilized Enzymes." In Uses of Immobilized Biological Compounds, 151–60. Dordrecht: Springer Netherlands, 1993. http://dx.doi.org/10.1007/978-94-011-1932-0_15.

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Silva, Ana Catarina, Cládia Pina Costa, Hugo Almeida, João Nuno Moreira, and José Manuel Sousa Lobo. "Hormones, Blood Products, and Therapeutic Enzymes." In Current Applications of Pharmaceutical Biotechnology, 115–53. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/10_2019_111.

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Taipa, M. Ângela, Pedro Fernandes, and Carla C. C. R. de Carvalho. "Production and Purification of Therapeutic Enzymes." In Advances in Experimental Medicine and Biology, 1–24. Singapore: Springer Singapore, 2019. http://dx.doi.org/10.1007/978-981-13-7709-9_1.

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Torchilin, Vladimir P. "Therapeutic Immobilized Enzymes for Parenteral Application." In Progress in Clinical Biochemistry and Medicine, 29–124. Berlin, Heidelberg: Springer Berlin Heidelberg, 1991. http://dx.doi.org/10.1007/978-3-642-75821-8_4.

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Sabu, Abdulhameed, K. Madhavan Nampoothiri, and Ashok Pandey. "L-Glutaminase as a Therapeutic Enzyme of Microbial Origin." In Microbial Enzymes and Biotransformations, 75–90. Totowa, NJ: Humana Press, 2005. http://dx.doi.org/10.1385/1-59259-846-3:075.

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Lu, Anthony Y. H. "Therapeutic Agents and Cytochrome P450." In Molecular Aspects of Oxidative Drug Metabolizing Enzymes, 503–13. Berlin, Heidelberg: Springer Berlin Heidelberg, 1995. http://dx.doi.org/10.1007/978-3-642-79528-2_24.

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Conference papers on the topic "Therapeutic enzymes"

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O’Toole, S., H. Melarcode, S. Elbaruni, F. AbuSaadeh, M. Ward, M. Gallagher, L. Norris, S. Gray, J. O`Leary, and B. Mohamed. "EP926 PAD enzymes as a candidate therapeutic target in ovarian cancer." In ESGO Annual Meeting Abstracts. BMJ Publishing Group Ltd, 2019. http://dx.doi.org/10.1136/ijgc-2019-esgo.972.

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Vazquez, Louis C., Erik Hagel, Bradley J. Willenberg, Christopher D. Batich, and Malisa Sarntinoranont. "Effect of Polymer Coated Needles on Infusate Backflow During Convection-Enhanced Delivery." In ASME 2010 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2010. http://dx.doi.org/10.1115/sbc2010-19557.

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Currently, many central nervous system disorders cannot be treated effectively using conventional drug delivery methods such as oral and intravenous drug administration. Therapeutic agents for such disorders often contain polar proteins with high molecular weight compounds (i.e. enzymes, antibodies and gene vectors) that are too large to diffuse through the tight junctions of the blood brain barrier (BBB) [1]. Moreover, it has been shown that low molecular weight compounds, though highly diffusive within brain tissue and tumors, have a limited distribution of just a few millimeters from the site of delivery due to loss via capillaries [1]. Direct infusion into the brain using convection-enhanced delivery (CED) as a supplement to diffusion is a technique that can circumvent these limitations by allowing one to utilize bulk flow to achieve much greater drug concentrations throughout the targeted area [1].
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Ofosu, F. A., G. J. Modi, M. R. Buchanan, J. Hirsh, and M. A. Blajchman. "HEPARIN IS NOT AN EFFICIENT INHIBITOR OF THE FACTOR Xa-DEPENDENT ACTIVATION OF FACTOR V AND FACTOR VIII." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642931.

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We have previously proposed that the steps in coagulation most sensitive to inhibition by heparin are the thrombin-dependent activation of factor V and factor VIII. This observation was based on the demonstration that therapeutic concentrations of heparin or 1μM of the thrombin specific inhibitor, phe-pro-arg CH2Cl (PPACK) completely inhibited the activation of prothrombin when contact-activated plasma (CAP) was recalcified for up to 1 min. Under similar conditions, heparin and PPACK only partially inhibited the activation of factor X. Moreover, the addition of thrombin (lOnM) to CAP 1 min before that of heparin or PPACK reversed their inhibitory effects. We now provide further support for our hypothesis by showing that when the activity of thrombin is suppressed by heparin or PPACK, efficient activation of radiolabelled prothrombin occurs only when the factor Xa then present activates factor V and factor VIII. We compared the effects of HEP of PPACK on the following four systems for initiating the activation of prothrombin: (1) CAP; (2) CAP + lOnM thrombin; (3) CAP + InM Xa and (4) unactivated plasma + InM Xa + InM Va + coagulant phospholipids. In each system, the enzymes were added 1 min before the heparin or PPACK. In the absence of heparin or PPACK, all four systems generated the same amount of thrombin activity in 45s. Complete inhibition of prothrombin activation by heparin and PPACK was observed only in system 1 which did not contain exogenous thrombin or factor Xa. No inhibition by heparin or PPACK was observed when thrombin or factor Xa was added to CAP in systems (2) and (3). Only partial inhibition was observed in system (4) which contained exogenous prothrombi-nase complex. Factor Xa thus provides an effective by-pass mechanism for the activation of factor VIII and factor V in plasma containing therapeutic concentrations of heparin. Our data provide further evidence that the heparin-antithrombin III system is not effective in inactivating factor Xa. These results support the hypothesis that in unactivated normal plasma, the primary anticoagulant effect of heparin is the inhibition of the thrombin-dependent activation of factor V and factor VIII.
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Agouni, Abdelali, Duck Y. Lee, Assaad A. Eid, Yves Gorin, and Kumar Sharma. "The Protective Role of Sestrin2 in High Fat Diet-Induced Nephropathy." In Qatar University Annual Research Forum & Exhibition. Qatar University Press, 2020. http://dx.doi.org/10.29117/quarfe.2020.0134.

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Introduction: Obesity is a major risk factor for type-2 diabetes predisposing patients to diabetic nephropathy (DN), the leading cause of end-stage renal failure. Glomerular injury is a prominent pathological feature of DN. Sestrin2 (Sesn2) is a stress-induced protein, but its role in DN has not been investigated. Therefore, we have determined the impact of Sesn2 deletion in a mouse model of obesityinduced nephropathy. Materials and methods: We examined the effects of Sesn2-deficiency in a longterm (22 weeks) mouse model of high fat diet (HFD)-induced obesity on glomerular structure. The severity of renal injury and fibrosis in wild type (Sesn2+/+) mice (fed HFD or chow diets) was compared to that in Sesn2-deficient mice (Sesn2-/- ) fed HFD or chow diets. Animal work was carried out under an IACUC-approved protocol. Results: Data showed that Sesn2 ablation exacerbated HFD-induced glomerular fibrotic injury as evidenced by mesangial matrix hypertrophy and accumulation of both fibronectin and collagen IV. Western blot analysis revealed that HFD- or chow-fed Sesn2-/- mice exhibited higher protein expression of key lipogenic enzymes, fatty acid translocase CD36 (an indicator of lipid uptake), fatty acid synthase and ATP citrate lyase. Sesn2-deficiency in obese mice resulted in podocyte loss as indicated by reduced expression of synaptopodin. Glomerular lesions like those observed in HFD-fed wild-type mice were detected in Sesn2-/-mice fed a chow diet, indicating that the basal deletion of Sesn2 is deleterious by itself. Conclusions: We provide the first evidence that Sesn2 is renoprotective in obesity-induced nephropathy by diminishing lipid accumulation and blocking excessive lipid uptake and de novo lipid synthesis. Understanding the protective of Sesn2 should yield novel therapeutic interventions to effectively preserve glomerular function in obesity and diabetes.
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Turina, E. L., S. G. Efimenko, Yu A. Kornev, and A. P. Liksutina. "Results of Сamelina oil assessment." In РАЦИОНАЛЬНОЕ ИСПОЛЬЗОВАНИЕ ПРИРОДНЫХ РЕСУРСОВ В АГРОЦЕНОЗАХ. Federal State Budget Scientific Institution “Research Institute of Agriculture of Crimea”, 2020. http://dx.doi.org/10.33952/2542-0720-15.05.2020.35.

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Camelina sativa (L.) Crantz – is an annual oilseed crop in the family Brassicaceae. The aim of the research was to study oil obtained from camelina seeds cultivated in the Crimea. Determination of fatty acid composition was carried out on the gas chromatograph “Хроматэк – Кристалл 5000” (Hromatek - Crystal 5000); automatic dosing unit ДАЖ-2М (DAJ- 2M); capillary column SolGelWax 30m × 0.25 mm × 0.5 μm; carrier gas – helium; speed – 22 centimeters per second; programming temperature –178–230 °С. The preparation of fatty acid methyl esters (FAMEs) using gas-liquid chromatography (GC) was performed in line with the methodology. The content of biologically active substances (tocopherols) in Camelina sativa oil was carried out using thin-layer chromatography (TLC) and spectroscopy. To obtain biofuel, we used the transesterification of triglyceride (or triacylglycerols) of camelina oil with methyl alcohol using potassium hydroxide (or sodium) as a homogeneous catalyst, as well as active metal oxides or enzymes (regiospecific lipase) as heterogeneous catalysts. Camelina sativa oil, obtained from false flax cultivated in the Crimea, should be used, first of all, to ensure healthy, dietary and therapeutic nutrition of the locals and tourists. Since, depending on the variety and the amount of precipitation, it contains 17.89-19.66% of linoleic acid; 33.02-37.06% of linolenic acid; not more than 3.05% of erucic acid. Furthermore, the ratio of omega-3 to omega-6 fatty acids varies from 1.7: 1.0 to 2.2: 1.0 even in wet years. The oil from the winter camelina seeds (‘Penzyak’ variety) in its composition and properties is suitable for the synthesis of biodiesel by the methanolysis reaction using a homogeneous alkaline catalyst. The physical and chemical properties of the obtained biodiesel are similar to those of sunflower or rapeseed oils.
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Chen, Liqiang, Riccardo Petrelli, Krzysztof Felczak, Magda Olesiak, Eric M. Bennett, Giulio Magni, and Krzysztof W. Pankiewicz. "Novel cofactor-type inhibitors of NAD-dependent enzymes. NAD-based therapeutics." In XIVth Symposium on Chemistry of Nucleic Acid Components. Prague: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 2008. http://dx.doi.org/10.1135/css200810071.

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Berger, C., A. Pilch, J. Ruppert, FP Armbruster, and J. Stein. "An enzyme-linked immunosorbent assay for therapeutic drug monitoring of Golimumab." In Viszeralmedizin 2017. Georg Thieme Verlag KG, 2017. http://dx.doi.org/10.1055/s-0037-1604810.

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Lee, David L., Hsiao-ling M. Chin, Christopher G. Knudsen, George L. Mayers, David S. Rose, Roy K. Skogstrom, Timothy Palzkill, et al. "Peptide-based scaffolds for in vivo immobilization and enzyme attachment in therapeutic applications." In Molecular and Nano Machines III, edited by Zouheir Sekkat and Takashige Omatsu. SPIE, 2020. http://dx.doi.org/10.1117/12.2566895.

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Rohyami, Yuli, Rafika Debby Anjani, and Napthalina Putri Purwanti. "The influence of Saccharomyces cerevisiae enzyme ratio on preparation virgin coconut oil for candidate in-house reference materials." In PROCEEDINGS FROM THE 14TH INTERNATIONAL SYMPOSIUM ON THERAPEUTIC ULTRASOUND. Author(s), 2017. http://dx.doi.org/10.1063/1.4978159.

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R., Halimahtussadiyah, Muh Natsir, Desy Kurniawati, and Sukma Puspita Utamy. "Isolation and identification of chitinolytic bacteria of pohara river of South East Sulawesi and the optimization production of chitinase enzyme." In PROCEEDINGS FROM THE 14TH INTERNATIONAL SYMPOSIUM ON THERAPEUTIC ULTRASOUND. Author(s), 2017. http://dx.doi.org/10.1063/1.4978135.

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Reports on the topic "Therapeutic enzymes"

1

Chen, Shuo. Anti-Androgen Receptor RNA Enzyme as a Novel Therapeutic Agent for Prostate Cancer In Vivo. Fort Belvoir, VA: Defense Technical Information Center, August 2006. http://dx.doi.org/10.21236/ada462865.

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