Pub Date : 2023-06-01DOI: 10.55959/msu0579-9384-2-2023-64-1-35-48
OLEG V. TINKOV, VENIAMIN YU. GRIGOREV, LYUDMILA D. GRIGOREVA
Histone deacetylase inhibitors are the most important class of drugs for the treatment of oncologies and other diseases due to their effect on cell growth, differentiation and apoptosis. Among the known eighteen histone deacetylases, Histone deacetylase 6 (HDAC6), which is involved in oncogenesis, cell survival, and cancer cell metastasis, is of high importance. Using 2D molecular descriptors RDKit, simplex descriptors, as well as methods of Random Forest (RF), Gradient Boosting (GBM), Support vectors (SVM), a number of adequate classi cation models of Quantitative Structure-Activity Relationship (QSAR) are proposed. For the models constructed using simplex descriptors, a structural interpretation was carried out, which made it possible to describe molecular fragments that increase and decrease the activity of HDAC6 inhibitors. The results of the structural interpretation were used for the rational molecular design of potential HDAC6 inhibitors, for which ADMET properties were also evaluated. Models built using 2D RDKit descriptors are freely available on the github platform (https://github.com/ovttiras/HDAC6-inhibitors).
{"title":"QSAR ANALYSIS OF HDAC6 INHIBITORS","authors":"OLEG V. TINKOV, VENIAMIN YU. GRIGOREV, LYUDMILA D. GRIGOREVA","doi":"10.55959/msu0579-9384-2-2023-64-1-35-48","DOIUrl":"https://doi.org/10.55959/msu0579-9384-2-2023-64-1-35-48","url":null,"abstract":"Histone deacetylase inhibitors are the most important class of drugs for the treatment of oncologies and other diseases due to their effect on cell growth, differentiation and apoptosis. Among the known eighteen histone deacetylases, Histone deacetylase 6 (HDAC6), which is involved in oncogenesis, cell survival, and cancer cell metastasis, is of high importance. Using 2D molecular descriptors RDKit, simplex descriptors, as well as methods of Random Forest (RF), Gradient Boosting (GBM), Support vectors (SVM), a number of adequate classi cation models of Quantitative Structure-Activity Relationship (QSAR) are proposed. For the models constructed using simplex descriptors, a structural interpretation was carried out, which made it possible to describe molecular fragments that increase and decrease the activity of HDAC6 inhibitors. The results of the structural interpretation were used for the rational molecular design of potential HDAC6 inhibitors, for which ADMET properties were also evaluated. Models built using 2D RDKit descriptors are freely available on the github platform (https://github.com/ovttiras/HDAC6-inhibitors).","PeriodicalId":23660,"journal":{"name":"Vestnik Moskovskogo Universiteta Seriya 2 Khimiya","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135673788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.55959/msu0579-9384-2-2023-64-2-99-111
ANASTASIA A. POMETUN, ANNA A. SHIROKOVA, GALANICHEVA NATALIA P., LEONID A. SHAPOSHNIKOV, DENIS L. ATROSHENKO, EVGENII V. POMETUN, VLADIMIR I. TISHKOV, SVYATOSLAV S. SAVIN
NAD+-dependent formate dehydrogenase (FDH, EC 1.2.1.2) from methylotrophic bacterium Pseudomonas sp.101 (PseFDH) has one of the highest thermal stability among all known enzymes of this group. The introduction of a number of amino acid substitutions into PseFDH made it possible to obtain a multipoint mutant PseFDH SM4S enzyme with even higher temperature and chemical stability. Previously, we showed that the introduction of additional single point replacements S131A, or S160A, or E170D into PseFDH SM4S led to further stabilization of the enzyme. In this work, based on the PseFDH SM4S S131A mutant, new mutant FDHs obtained, in which, compared to PseFDH SM4S, we added double S131A/E170D (M2), triple S131A/S160A/E170D (M3) and quadruple S131A/S160A/ E170D/S145A (PseFDH SM4A M3) amino acids replacements. The new PseFDH mutants were overexpressed in E. coli cells, puri ed and characterized. The S131A/E170D and S131A/S160A/E170D changes provided further improving thermal stability. The introduction of the S145A substitution into PseFDH SM4S M4 leads to a signi cant decrease in KMNAD+ and KMHCOO- while maintaining the catalytic constant at the same level. This mutant form can be successfully used in NADH regeneration systems, as well as for the detection of NAD+ and formate in biological systems.
{"title":"HIGHLY STABLE MUTANT BACTERIAL FORMAT DEHYDROGENASE WITH IMPROVED CATALYTIC PROPERTIES","authors":"ANASTASIA A. POMETUN, ANNA A. SHIROKOVA, GALANICHEVA NATALIA P., LEONID A. SHAPOSHNIKOV, DENIS L. ATROSHENKO, EVGENII V. POMETUN, VLADIMIR I. TISHKOV, SVYATOSLAV S. SAVIN","doi":"10.55959/msu0579-9384-2-2023-64-2-99-111","DOIUrl":"https://doi.org/10.55959/msu0579-9384-2-2023-64-2-99-111","url":null,"abstract":"NAD+-dependent formate dehydrogenase (FDH, EC 1.2.1.2) from methylotrophic bacterium Pseudomonas sp.101 (PseFDH) has one of the highest thermal stability among all known enzymes of this group. The introduction of a number of amino acid substitutions into PseFDH made it possible to obtain a multipoint mutant PseFDH SM4S enzyme with even higher temperature and chemical stability. Previously, we showed that the introduction of additional single point replacements S131A, or S160A, or E170D into PseFDH SM4S led to further stabilization of the enzyme. In this work, based on the PseFDH SM4S S131A mutant, new mutant FDHs obtained, in which, compared to PseFDH SM4S, we added double S131A/E170D (M2), triple S131A/S160A/E170D (M3) and quadruple S131A/S160A/ E170D/S145A (PseFDH SM4A M3) amino acids replacements. The new PseFDH mutants were overexpressed in E. coli cells, puri ed and characterized. The S131A/E170D and S131A/S160A/E170D changes provided further improving thermal stability. The introduction of the S145A substitution into PseFDH SM4S M4 leads to a signi cant decrease in KMNAD+ and KMHCOO- while maintaining the catalytic constant at the same level. This mutant form can be successfully used in NADH regeneration systems, as well as for the detection of NAD+ and formate in biological systems.","PeriodicalId":23660,"journal":{"name":"Vestnik Moskovskogo Universiteta Seriya 2 Khimiya","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135726826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.55959/msu0579-9384-2-2023-64-2-195-202
NIKOLAY V. RASTRIGA, DARIA A. GASANOVA, PAVEL A. LEVASHOV
For human and chicken lysozyme , the relationship between changes in the parameters of enzyme adsorption on living Escherichia coli bacterial cells and the value of its effective bacteriolytic activity in the presence of glycine and charged amino acids was studied . It has been shown for both human and chicken lysozyme that free amino acids added to a concentration of 1.5 mM for glycine or 5.0 mM for glutamate, aspartate, histidine, arginine, and lysine reduce the desorption constant of the enzyme on bacterial cells to 1.4-2.0 times. At the same time, an increase in the bacteriolytic activity of lysozyme is also observed in 1.5-1.9 times. Thus, the enhancement of antibacterial activity in the presence of glycine and charged amino acids can be explained by an improvement in the productive sorption of the enzyme on the substrate, bacterial cells.
{"title":"ADSORPTION OF LYSOZYME ON LIVING CELLS OF ESCHERICHIA COLI AND ITS BACTERIOLYTIC ACTIVITY IN THE PRESENCE OF GLYCINE AND CHARGED AMINO ACIDS","authors":"NIKOLAY V. RASTRIGA, DARIA A. GASANOVA, PAVEL A. LEVASHOV","doi":"10.55959/msu0579-9384-2-2023-64-2-195-202","DOIUrl":"https://doi.org/10.55959/msu0579-9384-2-2023-64-2-195-202","url":null,"abstract":"For human and chicken lysozyme , the relationship between changes in the parameters of enzyme adsorption on living Escherichia coli bacterial cells and the value of its effective bacteriolytic activity in the presence of glycine and charged amino acids was studied . It has been shown for both human and chicken lysozyme that free amino acids added to a concentration of 1.5 mM for glycine or 5.0 mM for glutamate, aspartate, histidine, arginine, and lysine reduce the desorption constant of the enzyme on bacterial cells to 1.4-2.0 times. At the same time, an increase in the bacteriolytic activity of lysozyme is also observed in 1.5-1.9 times. Thus, the enhancement of antibacterial activity in the presence of glycine and charged amino acids can be explained by an improvement in the productive sorption of the enzyme on the substrate, bacterial cells.","PeriodicalId":23660,"journal":{"name":"Vestnik Moskovskogo Universiteta Seriya 2 Khimiya","volume":"8 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135722763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.55959/msu0579-9384-2-2023-64-1-11-18
Olga I. Vernaya, Alexey S. Shumilkin, Darya L. Karlova, Anna S. Shevchenko, Alina A. Makeeva, Andrey V. Shabatin, Alexandr M. Semenov, Tatiana I. Shabatina, Mikhai Ya. Melnikov
Cryoforming of gelatin systems with the antibacterial drug dioxidine was carried out. The paper considers the effect of system synthesis conditions (gelatin concentration in the precursor solution) on their structural characteristics, antibacterial activity, and drug release time. The composition and structure of the dioxidine/gelatin and dioxidine/hydrolyzed collagen systems were characterized by SEM, IR and UV spectroscopy. The disk diffusion method was used to determine the antibacterial activity of the obtained systems against E. coli and S. aureus.
{"title":"CRYOFORMATION AND PROPERTIES OF DIOXIDIN/GELATIN SYSTEMS","authors":"Olga I. Vernaya, Alexey S. Shumilkin, Darya L. Karlova, Anna S. Shevchenko, Alina A. Makeeva, Andrey V. Shabatin, Alexandr M. Semenov, Tatiana I. Shabatina, Mikhai Ya. Melnikov","doi":"10.55959/msu0579-9384-2-2023-64-1-11-18","DOIUrl":"https://doi.org/10.55959/msu0579-9384-2-2023-64-1-11-18","url":null,"abstract":"Cryoforming of gelatin systems with the antibacterial drug dioxidine was carried out. The paper considers the effect of system synthesis conditions (gelatin concentration in the precursor solution) on their structural characteristics, antibacterial activity, and drug release time. The composition and structure of the dioxidine/gelatin and dioxidine/hydrolyzed collagen systems were characterized by SEM, IR and UV spectroscopy. The disk diffusion method was used to determine the antibacterial activity of the obtained systems against E. coli and S. aureus.","PeriodicalId":23660,"journal":{"name":"Vestnik Moskovskogo Universiteta Seriya 2 Khimiya","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135674265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.55959/msu0579-9384-2-2023-64-2-72-84
Vladimir I. Tishkov, Michail D. Shelomov, Anastaiya A. Pometun, Svyatoslav S. Savin, Denis L. Atroshenko
D-amino acid oxidase (DAAO) plays an important role in the functioning of both prokaryotes and eukaryotes. DAAO is increasingly being used in practice, including for the determination of D-amino acids in complex samples, including human tissues and fl uids. There are generally two types of DAAO in all organisms. The fi rst type is an enzyme highly specifi c for D-aspartate and has its own name D-aspartate oxidase (DASPO). DAAO of the second type is characterized by a wide spectrum of substrate specificity, with preference for one or another D-amino acid varying from source to source. The activity of DAAO with a large number of substrates greatly complicates the selective determination of a particular D-amino acid. The problem is often solved by choosing an enzyme that, under the conditions of analysis, has low or no activity with other D-amino acids present in the sample. For the convenience of selecting a particular enzyme, we have collected and analyzed literature data on the catalytic parameters of known DAAOs with the most important D-amino acids. In addition, similar data are presented for novel recombinant DAAOs from the methylotrophic yeast Ogataea parapolymorpha DL-1. Analysis of the data shows that, with the D-amino acid series, the new OpaDASPO and OpaDAAO have the highest catalytic parameters.
{"title":"PHYSIOLOGICAL ROLE OF D-AMINO ACIDS AND BIOANALYTICAL POTENTIAL OF D-AMINO ACID OXIDASES","authors":"Vladimir I. Tishkov, Michail D. Shelomov, Anastaiya A. Pometun, Svyatoslav S. Savin, Denis L. Atroshenko","doi":"10.55959/msu0579-9384-2-2023-64-2-72-84","DOIUrl":"https://doi.org/10.55959/msu0579-9384-2-2023-64-2-72-84","url":null,"abstract":"D-amino acid oxidase (DAAO) plays an important role in the functioning of both prokaryotes and eukaryotes. DAAO is increasingly being used in practice, including for the determination of D-amino acids in complex samples, including human tissues and fl uids. There are generally two types of DAAO in all organisms. The fi rst type is an enzyme highly specifi c for D-aspartate and has its own name D-aspartate oxidase (DASPO). DAAO of the second type is characterized by a wide spectrum of substrate specificity, with preference for one or another D-amino acid varying from source to source. The activity of DAAO with a large number of substrates greatly complicates the selective determination of a particular D-amino acid. The problem is often solved by choosing an enzyme that, under the conditions of analysis, has low or no activity with other D-amino acids present in the sample. For the convenience of selecting a particular enzyme, we have collected and analyzed literature data on the catalytic parameters of known DAAOs with the most important D-amino acids. In addition, similar data are presented for novel recombinant DAAOs from the methylotrophic yeast Ogataea parapolymorpha DL-1. Analysis of the data shows that, with the D-amino acid series, the new OpaDASPO and OpaDAAO have the highest catalytic parameters.","PeriodicalId":23660,"journal":{"name":"Vestnik Moskovskogo Universiteta Seriya 2 Khimiya","volume":"20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135727040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PD-L1 (Programmed death-ligand 1), a membrane protein of the immunoglobulin superfamily, is one of the targets for cancer immunotherapy. A panel of 14 cancer cell cultures with different constitutive PD-L1 expression level was formed and characterized. The panel is recommended for preclinical studies of a cytostatic drug effect on PD-L1 expression and for predicting the ef cacy of their combination with immune checkpoint inhibitors.
{"title":"TUMOR CELL PANEL WITH CHARACTERIZED EXPRESSION OF PD-L1 FOR PRECLINICAL STUDIES OF ANTICANCER DRUGS AND IMMUNE CHECKPOINT INHIBITORS INTERACTION","authors":"T.A. Bogush, A.A. Basharin, A.M. Scherbakov, K.I. Chandran, A.L. Mikhailova, I.P. Romanov, E.A. Bogush, V.S. Kosorukov","doi":"10.55959/msu0579-9384-2-2023-64-1-26-34","DOIUrl":"https://doi.org/10.55959/msu0579-9384-2-2023-64-1-26-34","url":null,"abstract":"PD-L1 (Programmed death-ligand 1), a membrane protein of the immunoglobulin superfamily, is one of the targets for cancer immunotherapy. A panel of 14 cancer cell cultures with different constitutive PD-L1 expression level was formed and characterized. The panel is recommended for preclinical studies of a cytostatic drug effect on PD-L1 expression and for predicting the ef cacy of their combination with immune checkpoint inhibitors.","PeriodicalId":23660,"journal":{"name":"Vestnik Moskovskogo Universiteta Seriya 2 Khimiya","volume":"16 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135675760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.55959/msu0579-9384-2-2023-64-1-49-59
VASILY G. AMELIN, SHOGAH ZEN ALABDEN CHALAWI, DMITRY S. BOLSHAKOV
The possibility of identi cation and authentication of cow’s milk powder by the method of chemical colorimetry of the samples’ own uorescence using a smartphone camera and chemometric analysis is shown. A fundamental test device for direct colorimetric analysis of powdered milk is proposed, excluding the stage of sample preparation. Fluorescence excitation was carried out with a portable source of monochromatic UV radiation (λ = 365 nm). Colorimetric parameters of powdered milk uorescence in RGB space were recorded using a smartphone camera. We used chemometric processing of the calculated analytical signal, which made it possible to reduce the analysis time and visualize the study data. The evaluation of the data array of uorescence colorimetric parameters (RGB) was carried out by principal component analysis (PCA) and hierarchical clustering analysis (HCA) using the XLSTAT software.
{"title":"IDENTIFICATION AND AUTHENTICATION OF COW’S MILK POWDER USING A SMARTPHONE AND CHEMOMETRIC ANALYSIS","authors":"VASILY G. AMELIN, SHOGAH ZEN ALABDEN CHALAWI, DMITRY S. BOLSHAKOV","doi":"10.55959/msu0579-9384-2-2023-64-1-49-59","DOIUrl":"https://doi.org/10.55959/msu0579-9384-2-2023-64-1-49-59","url":null,"abstract":"The possibility of identi cation and authentication of cow’s milk powder by the method of chemical colorimetry of the samples’ own uorescence using a smartphone camera and chemometric analysis is shown. A fundamental test device for direct colorimetric analysis of powdered milk is proposed, excluding the stage of sample preparation. Fluorescence excitation was carried out with a portable source of monochromatic UV radiation (λ = 365 nm). Colorimetric parameters of powdered milk uorescence in RGB space were recorded using a smartphone camera. We used chemometric processing of the calculated analytical signal, which made it possible to reduce the analysis time and visualize the study data. The evaluation of the data array of uorescence colorimetric parameters (RGB) was carried out by principal component analysis (PCA) and hierarchical clustering analysis (HCA) using the XLSTAT software.","PeriodicalId":23660,"journal":{"name":"Vestnik Moskovskogo Universiteta Seriya 2 Khimiya","volume":"43 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135673782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.55959/msu0579-9384-2-2023-64-2-152-162
MARIA K. KOSHKINA, EGOR P. SERGEYEV, TIMOFEY A. FEDOROV, MICHAEL D. SHELOMOV, ANASTASIA A. POMETUN, SVYATOSLAV S. SAVIN, VLADIMIR I. TISHKOV, DENIS L. ATROSHENKO
Our earlier annotation of genome of the yeast Ogataea parapolymorpha DL-1 made it possible to identify ve genes of potential D-amino acids oxidases. All opadaao1 - opadaao5 genes were cloned and expressed in E. coli. Four OpaDAAO1- OpaDAAO4 enzymes were obtained in highly puri ed form and their catalytic properties were studied. It was found that among all DAAOs described in the literature so far, the enzyme OpaDAAO1 has the highest catalytic constant kcat with D-Ala, which makes it promising for practical applications. However, in addition to good catalytic parameters, effective application of the enzyme in practice requires high stability and knowledge of the inactivation mechanism, including at elevated temperatures. In this work we studied the effect of elevated temperatures on the stability of OpaDAAO1. The enzyme was shown to have high thermal stability in comparison with majority of other D-amino acid oxidases. The kinetics of OpaDAAO1 inactivation at different temperatures, initial concentrations of the enzyme, and in the presence of exogenous FAD were studied. A possible kinetic scheme of inactivation was proposed based on the data obtained.
{"title":"KINETICS OF THERMOINACTIVATION OF D-AMINO ACID OXIDASE OPADAAO1 FROM THE OGATAEA PARAPOLYMORPHA DL-1 YEAST","authors":"MARIA K. KOSHKINA, EGOR P. SERGEYEV, TIMOFEY A. FEDOROV, MICHAEL D. SHELOMOV, ANASTASIA A. POMETUN, SVYATOSLAV S. SAVIN, VLADIMIR I. TISHKOV, DENIS L. ATROSHENKO","doi":"10.55959/msu0579-9384-2-2023-64-2-152-162","DOIUrl":"https://doi.org/10.55959/msu0579-9384-2-2023-64-2-152-162","url":null,"abstract":"Our earlier annotation of genome of the yeast Ogataea parapolymorpha DL-1 made it possible to identify ve genes of potential D-amino acids oxidases. All opadaao1 - opadaao5 genes were cloned and expressed in E. coli. Four OpaDAAO1- OpaDAAO4 enzymes were obtained in highly puri ed form and their catalytic properties were studied. It was found that among all DAAOs described in the literature so far, the enzyme OpaDAAO1 has the highest catalytic constant kcat with D-Ala, which makes it promising for practical applications. However, in addition to good catalytic parameters, effective application of the enzyme in practice requires high stability and knowledge of the inactivation mechanism, including at elevated temperatures. In this work we studied the effect of elevated temperatures on the stability of OpaDAAO1. The enzyme was shown to have high thermal stability in comparison with majority of other D-amino acid oxidases. The kinetics of OpaDAAO1 inactivation at different temperatures, initial concentrations of the enzyme, and in the presence of exogenous FAD were studied. A possible kinetic scheme of inactivation was proposed based on the data obtained.","PeriodicalId":23660,"journal":{"name":"Vestnik Moskovskogo Universiteta Seriya 2 Khimiya","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135777150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.55959/msu0579-9384-2-2023-64-2-141-151
EKATERINA V. POPOVA, VICTORIA E. TIKHOMIROVA, OLGA V. BEZNOS, NATALIA B. CHESNOKOVA, YURI V. GRIGORIEV, OLGA A. KOST
The effectiveness of drug penetration into the inner tissues of the eye is signi cantly limited by the barrier effect of the cornea and by the washing out of a drug with tear uid. To increase the bioavailability of the drug, it was proposed to include the drug in chitosan particles formed by two types of chitosan - 5 kDa chitosan and 72 kDa glycol-chitosan. Chitosan particles with incorporated angiotensin-converting enzyme inhibitor enalaprilat, capable to reduce intraocular pressure, were characterized by dynamic light scattering and scanning electron microscopy. Particles formed by 5 kDa chitosan had an average hydrodynamic diameter of 85-125 nm and a positive ζ-potential of +21±3 mV, while particles formed by 72 kDa glycol-chitosan were 440-480 nm by size and had ζ-potential of +10±2 mV. The percentage of inclusion of enalaprilat in chitosan particles was 25% and 40%, respectively. In vivo experiments have shown that the inclusion of the drug in chitosan particles increased the retention time of enalaprilat in the lacrimal uid of rabbits.
{"title":"CHITOSAN NANOPARTICLES - THE DRUG DELIVERY SYSTEM TO THE ANTERIOR SEGMENT OF THE EYE","authors":"EKATERINA V. POPOVA, VICTORIA E. TIKHOMIROVA, OLGA V. BEZNOS, NATALIA B. CHESNOKOVA, YURI V. GRIGORIEV, OLGA A. KOST","doi":"10.55959/msu0579-9384-2-2023-64-2-141-151","DOIUrl":"https://doi.org/10.55959/msu0579-9384-2-2023-64-2-141-151","url":null,"abstract":"The effectiveness of drug penetration into the inner tissues of the eye is signi cantly limited by the barrier effect of the cornea and by the washing out of a drug with tear uid. To increase the bioavailability of the drug, it was proposed to include the drug in chitosan particles formed by two types of chitosan - 5 kDa chitosan and 72 kDa glycol-chitosan. Chitosan particles with incorporated angiotensin-converting enzyme inhibitor enalaprilat, capable to reduce intraocular pressure, were characterized by dynamic light scattering and scanning electron microscopy. Particles formed by 5 kDa chitosan had an average hydrodynamic diameter of 85-125 nm and a positive ζ-potential of +21±3 mV, while particles formed by 72 kDa glycol-chitosan were 440-480 nm by size and had ζ-potential of +10±2 mV. The percentage of inclusion of enalaprilat in chitosan particles was 25% and 40%, respectively. In vivo experiments have shown that the inclusion of the drug in chitosan particles increased the retention time of enalaprilat in the lacrimal uid of rabbits.","PeriodicalId":23660,"journal":{"name":"Vestnik Moskovskogo Universiteta Seriya 2 Khimiya","volume":"20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135164753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.55959/msu0579-9384-2-2023-64-1-19-25
ALEKSANDER YU. ERMILOV, YANA A. GROMOVA, TATIANA I. SHABATINA
The structural geometries of small copper clusters (Cu2, Cu3, Cu13) and of their complexes with Cholesterol (Ch) and Thio-Cholesterol (TCh) ligands were studied by DFT/ B3LYP5-method. General trends in evolution of complexes geometries and interaction energies of copper clusters of different nuclearity with Cholesterol (Thio-Cholesterol) ligands upon the copper cluster size (number of copper atoms). It was shown the signi cant deviations in the structures of copper clusters’ complexes with cholesteric ligands in comparison to the silver-containing complexes studied previously. Thus, in Ch-Cu13 complex structure icosahedral fragment is signi cantly elongated in 3-order axis direction. The biligand complex of icosahedral copper cluster (TCh)2Cu13 possessed the highest energy stability.
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