P. Bobrovsky, A. K. Larin, Nadezhda F. Polina, V. N. Lazarev
Human peptidoglycan recognition proteins (PGLYRPs) are the components of innate immunity that exhibit antibacterial activity. In this study a cell line secreting recombinant PGLYRP1 into a culture medium was obtained. Transcriptional profiling of cell lines expressing PGLYRP1 was performed at different stages of C. trachomatis infection. Differential gene expression was studied using the whole transcriptome profiling method on the HumanHT-12 v4 Expression BeadChip microchip using the Illumina Direct Hybridization Whole-Gene Expression Assay protocol. Sample clustering followed by bioinformatics analysis revealed about 100 differentially expressed genes in response to infection with C. trachomatis. PGLYRP1- expressing cells infected with C. trachomatis had a similar transcriptional profile as non-infected cells.
{"title":"Transcriptional Analysis of HELA Cells - Producers of the Recombinant Peptidoglycan Recognition Protein PGLYRP1 at Different Stages of the Chlamydia Trachomatis Infection Development","authors":"P. Bobrovsky, A. K. Larin, Nadezhda F. Polina, V. N. Lazarev","doi":"10.18097/bmcrm00113","DOIUrl":"https://doi.org/10.18097/bmcrm00113","url":null,"abstract":"Human peptidoglycan recognition proteins (PGLYRPs) are the components of innate immunity that exhibit antibacterial activity. In this study a cell line secreting recombinant PGLYRP1 into a culture medium was obtained. Transcriptional profiling of cell lines expressing PGLYRP1 was performed at different stages of C. trachomatis infection. Differential gene expression was studied using the whole transcriptome profiling method on the HumanHT-12 v4 Expression BeadChip microchip using the Illumina Direct Hybridization Whole-Gene Expression Assay protocol. Sample clustering followed by bioinformatics analysis revealed about 100 differentially expressed genes in response to infection with C. trachomatis. PGLYRP1- expressing cells infected with C. trachomatis had a similar transcriptional profile as non-infected cells.","PeriodicalId":286037,"journal":{"name":"Biomedical Chemistry: Research and Methods","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128087221","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}
Modern methods of analysis of drugs for their quantitative assessment are considered. Particular attention is paid to the electrochemical methods of drug registration, based on the reaction of electrooxidation of molecules. Systems and materials for modifying electrodes are described, as well as methods for producing modified electrodes for electrochemical reactions on the surface of electrodes. The authors present data on the electroanalysis of acetaminophen, diclofenac, ibuprofen, omeprazole, using electrodes modified with carbon nanomaterials based on carbon nanotubes and graphene. It was shown that electroanalytical methods allow the registration of therapeutic drugs in a wide range of detectable concentrations (0.1 μМ - 10 mM), which can be used to work with biological fluids (plasma, blood, urine), to conduct drug monitoring and study drug-drug interactions.
{"title":"Drug Analysis Methods","authors":"V. Shumyantseva, T. Bulko, P. I. Koroleva","doi":"10.18097/bmcrm00110","DOIUrl":"https://doi.org/10.18097/bmcrm00110","url":null,"abstract":"Modern methods of analysis of drugs for their quantitative assessment are considered. Particular attention is paid to the electrochemical methods of drug registration, based on the reaction of electrooxidation of molecules. Systems and materials for modifying electrodes are described, as well as methods for producing modified electrodes for electrochemical reactions on the surface of electrodes. The authors present data on the electroanalysis of acetaminophen, diclofenac, ibuprofen, omeprazole, using electrodes modified with carbon nanomaterials based on carbon nanotubes and graphene. It was shown that electroanalytical methods allow the registration of therapeutic drugs in a wide range of detectable concentrations (0.1 μМ - 10 mM), which can be used to work with biological fluids (plasma, blood, urine), to conduct drug monitoring and study drug-drug interactions.","PeriodicalId":286037,"journal":{"name":"Biomedical Chemistry: Research and Methods","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128165873","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}
It is stated in the literature that thrombosis in the chronic heart failure (CHF) patients may be caused by interaction of inflammation and platelets. The incidence of venous thromboembolism in heart failure patients is found to be the highest in the patients classified as NYHA IV. We aimed to test the hypothesis that prothrombotic state depends on inflammation. We have compared the C-reactive protein (CRP), fibrinogen concentration, platelet count (PLT), mean platelet volume (MPV) and platelet aggregation in CHF patients’ groups according to New York Heart Association (NYHA). 203 patients with CHF with reduced ejection fraction (systolic heart failure classes I‒IV according to NYHA) were included in the study. There were no statistically significant differences in fibrinogen concentration, CRP, PLT and platelet aggregation between the groups according to NYHA. The MPV was statistically significant higher in NYHA IV group than in NYHA III, NYHA II and NYHA I groups (10.86 ± 1.14 and 9.78 ± 1.21 and 9.65 ± 1.22 and 9.21 ± 0.59 respectively, p = 0.006). There was a weak correlation between CRP and PLT (r = 0.293, p = 0.010), and between MPV and fibrinogen concentration (r=0.205, p=0.012). There was a moderate correlation between MPV and NYHA (r = 0.361, p < 0.001) and between fibrinogen concentration and CRP (r = 0.381, p < 0.001). MPV rising in the patients’ groups and correlation between MPV and NYHA class, and plasma fibrinogen concentration, correlation between PLT and CRP, correlation between CRP and NT-proBNP concentration confirm, that low inflammation can take place in the MPV rising.
{"title":"Does Platelet and Inflammatory Readings Differ Between Chronic Heart Failure Patients‘ Groups According to NYHA Functional Classes?","authors":"A. Mongirdienė, J. Laukaitienė, V. Skipskis","doi":"10.18097/bmcrm00111","DOIUrl":"https://doi.org/10.18097/bmcrm00111","url":null,"abstract":"It is stated in the literature that thrombosis in the chronic heart failure (CHF) patients may be caused by interaction of inflammation and platelets. The incidence of venous thromboembolism in heart failure patients is found to be the highest in the patients classified as NYHA IV. We aimed to test the hypothesis that prothrombotic state depends on inflammation. We have compared the C-reactive protein (CRP), fibrinogen concentration, platelet count (PLT), mean platelet volume (MPV) and platelet aggregation in CHF patients’ groups according to New York Heart Association (NYHA). 203 patients with CHF with reduced ejection fraction (systolic heart failure classes I‒IV according to NYHA) were included in the study. There were no statistically significant differences in fibrinogen concentration, CRP, PLT and platelet aggregation between the groups according to NYHA. The MPV was statistically significant higher in NYHA IV group than in NYHA III, NYHA II and NYHA I groups (10.86 ± 1.14 and 9.78 ± 1.21 and 9.65 ± 1.22 and 9.21 ± 0.59 respectively, p = 0.006). There was a weak correlation between CRP and PLT (r = 0.293, p = 0.010), and between MPV and fibrinogen concentration (r=0.205, p=0.012). There was a moderate correlation between MPV and NYHA (r = 0.361, p < 0.001) and between fibrinogen concentration and CRP (r = 0.381, p < 0.001). MPV rising in the patients’ groups and correlation between MPV and NYHA class, and plasma fibrinogen concentration, correlation between PLT and CRP, correlation between CRP and NT-proBNP concentration confirm, that low inflammation can take place in the MPV rising.","PeriodicalId":286037,"journal":{"name":"Biomedical Chemistry: Research and Methods","volume":"11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116287222","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}
P. Ershov, L. Kaluzhskiy, E. Yablokov, A. S. Ivanov
The technology of dye-labeled proteins has many fields of application, especially in interactomics. The aim of this work was to adapt protocol of conjugation of low molecular weight (12 – 15 kDа) heme-containing proteins with fluorescein isothiocyanate, isomer I, (FITC) for subsequent protein-protein interaction studies. We have monitored the quality of FITC-labeling of the target protein and comparative assessment of its binding capacity. Using the cytochrome C (Mw 12 kDа) as an example, it has been shown that using the three step method approach including conventional spectrophotometry, capillary gel electrophoresis and SPR analysis it is possible to assess: (i) the capability of the FITC-labeled target protein to interact with its protein partner and protein material from tissue lysates, (ii) the fact of dye conjugation with the protein, and (iii) the quality of purification for final protein preparation from unreacted free dye molecules
{"title":"Quality Control Of FITC-labeled Proteins for Interactomics Investigations Using SDS Capillary Gel Electrophoresis and SPR Biosensor","authors":"P. Ershov, L. Kaluzhskiy, E. Yablokov, A. S. Ivanov","doi":"10.18097/bmcrm00112","DOIUrl":"https://doi.org/10.18097/bmcrm00112","url":null,"abstract":"The technology of dye-labeled proteins has many fields of application, especially in interactomics. The aim of this work was to adapt protocol of conjugation of low molecular weight (12 – 15 kDа) heme-containing proteins with fluorescein isothiocyanate, isomer I, (FITC) for subsequent protein-protein interaction studies. We have monitored the quality of FITC-labeling of the target protein and comparative assessment of its binding capacity. Using the cytochrome C (Mw 12 kDа) as an example, it has been shown that using the three step method approach including conventional spectrophotometry, capillary gel electrophoresis and SPR analysis it is possible to assess: (i) the capability of the FITC-labeled target protein to interact with its protein partner and protein material from tissue lysates, (ii) the fact of dye conjugation with the protein, and (iii) the quality of purification for final protein preparation from unreacted free dye molecules","PeriodicalId":286037,"journal":{"name":"Biomedical Chemistry: Research and Methods","volume":"33 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115056454","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}
D. Devyatkin, A. Molodchenkov, A. Lukin, Ya. S. Kim, A. Boyko, P. Karalkin, J. Chiang, G. D. Volkova, A. Lupatov
Cell-based immunotherapy is a promising approach for the treatment of chronic infections, autoimmune disorders, and malignant tumors. There are many strategies of cell-based immunotherapy of cancer; these include injection of various immune effector cells, propagated and «trained» in a cell culture. Alternatively, cells presenting tumor antigens on their surface in a form recognized by the immune system can be used to achieve a therapeutic effect. The research results in this field are presented in thousands of texts, and their manual analysis is very complicated. We have developed an approach for automated text analysis in this area of biomedical science. Here we present the first results of the automated analysis of the data extracted from abstracts of scientific articles available in PubMed. These results demonstrate the associations between types of tumors and the most commonly used methods of their cell-based immunotherapy.
{"title":"Towards Automated Meta-analysis of Biomedical Texts in the Field of Cell-based Immunotherapy","authors":"D. Devyatkin, A. Molodchenkov, A. Lukin, Ya. S. Kim, A. Boyko, P. Karalkin, J. Chiang, G. D. Volkova, A. Lupatov","doi":"10.18097/bmcrm00109","DOIUrl":"https://doi.org/10.18097/bmcrm00109","url":null,"abstract":"Cell-based immunotherapy is a promising approach for the treatment of chronic infections, autoimmune disorders, and malignant tumors. There are many strategies of cell-based immunotherapy of cancer; these include injection of various immune effector cells, propagated and «trained» in a cell culture. Alternatively, cells presenting tumor antigens on their surface in a form recognized by the immune system can be used to achieve a therapeutic effect. The research results in this field are presented in thousands of texts, and their manual analysis is very complicated. We have developed an approach for automated text analysis in this area of biomedical science. Here we present the first results of the automated analysis of the data extracted from abstracts of scientific articles available in PubMed. These results demonstrate the associations between types of tumors and the most commonly used methods of their cell-based immunotherapy.","PeriodicalId":286037,"journal":{"name":"Biomedical Chemistry: Research and Methods","volume":"37 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121467973","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}
D. Zhdanov, A. A. Plyasova, Y. Gladilina, M. Pokrovskaya, S. S. Alexandrova, N. Sokolov
Caspase-2 is a key enzyme thinvolved in induction of apoptosis. The caspase-2 level is regulated by alternative splicing (AS) of its mRNA. The aim of this work was to determine the ability of an oligonucleotide complementary to Casp-2 pre-mRNA to induce AS. This oligonucleotide blocked the binding of splicing-regulating proteins to their sites at the end of exon 9 of Casp-2 pre-mRNA, leading to induction of AS of Casp-2 mRNA. The decrease in expression of full-size active splice-variant (Casp-2L) and the increase the expression of a shortened variant (Casp-2S) was demonstrated in human T-cell lymphoma Jurkat cell line. The expression level of total Casp-2 remained unchanged. Disproportion of splice variants of Casp-2 led to inhibition of enzymatic activity of caspase-2.
{"title":"Inhibition of Caspase-2 Activity in Human Jurkat T-cell Lymphoma Cells by Splice Switching Oligonucleotide to its pre-mRNA","authors":"D. Zhdanov, A. A. Plyasova, Y. Gladilina, M. Pokrovskaya, S. S. Alexandrova, N. Sokolov","doi":"10.18097/bmcrm00108","DOIUrl":"https://doi.org/10.18097/bmcrm00108","url":null,"abstract":"Caspase-2 is a key enzyme thinvolved in induction of apoptosis. The caspase-2 level is regulated by alternative splicing (AS) of its mRNA. The aim of this work was to determine the ability of an oligonucleotide complementary to Casp-2 pre-mRNA to induce AS. This oligonucleotide blocked the binding of splicing-regulating proteins to their sites at the end of exon 9 of Casp-2 pre-mRNA, leading to induction of AS of Casp-2 mRNA. The decrease in expression of full-size active splice-variant (Casp-2L) and the increase the expression of a shortened variant (Casp-2S) was demonstrated in human T-cell lymphoma Jurkat cell line. The expression level of total Casp-2 remained unchanged. Disproportion of splice variants of Casp-2 led to inhibition of enzymatic activity of caspase-2.","PeriodicalId":286037,"journal":{"name":"Biomedical Chemistry: Research and Methods","volume":"72 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121878975","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}
Y. Tereshkina, M. A. Sanzhakov, L. Kostryukova, E. Korotkevich, A. Chistov, E. Tikhonova, V. N. Prozorovsky, O. Ipatova
The conditions for the preparation of a drug formulations based on the lipid derivative of sarcolysin embedded in phospholipid nanoparticles have been optimized. The drug is an ultra-thin emulsion with a light transmittance above 80% and a particle size of not more than 50 nm. It should be noted that 99% of the lipid derivative of sarcolysin are incorporated into phospholipid nanoparticles. Preservation of aggregation stability in the aquatic environment was observed for at least 2 days. In vitro experiments have shown that sarcolysin, introduced as a part of phospholipid nanoparticles, is distributed among lipoproteins and protein components of plasma. Moreover, the content of sarcolysin in all fractions involved in the transport of biologically active substances in the body, is significantly higher in case of prodrug administration (lipid derivative of sarcolysin) in the composition of phospholipid nanoparticles than, as compared with administration of a free form (pharmacological substances) to the incubation medium. The transformation of a prodrug into the drug sarcolysin occurs in the blood cells.
{"title":"Preparation and Properties of Antitumor Drug Based on Lipid Derivative of Sarcolysin","authors":"Y. Tereshkina, M. A. Sanzhakov, L. Kostryukova, E. Korotkevich, A. Chistov, E. Tikhonova, V. N. Prozorovsky, O. Ipatova","doi":"10.18097/bmcrm00098","DOIUrl":"https://doi.org/10.18097/bmcrm00098","url":null,"abstract":"The conditions for the preparation of a drug formulations based on the lipid derivative of sarcolysin embedded in phospholipid nanoparticles have been optimized. The drug is an ultra-thin emulsion with a light transmittance above 80% and a particle size of not more than 50 nm. It should be noted that 99% of the lipid derivative of sarcolysin are incorporated into phospholipid nanoparticles. Preservation of aggregation stability in the aquatic environment was observed for at least 2 days. In vitro experiments have shown that sarcolysin, introduced as a part of phospholipid nanoparticles, is distributed among lipoproteins and protein components of plasma. Moreover, the content of sarcolysin in all fractions involved in the transport of biologically active substances in the body, is significantly higher in case of prodrug administration (lipid derivative of sarcolysin) in the composition of phospholipid nanoparticles than, as compared with administration of a free form (pharmacological substances) to the incubation medium. The transformation of a prodrug into the drug sarcolysin occurs in the blood cells.","PeriodicalId":286037,"journal":{"name":"Biomedical Chemistry: Research and Methods","volume":"40 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121423641","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}
E. A. Kuvshinova, N. V. Petrakova, N. Sergeeva, V. Kirsanova, I. Sviridova, A. Teterina, V. Komlev, A. Kaprin
Recent approaches to the calcium phosphate (CaP) materials functionalization with drugs and biomolecules have been actively developed for bone defect reconstruction. However, the current techniques are low efficient in context of drug incorporation and non-controlled release from the materials. Eventually, continuous therapeutic effect in bone defect area couldn’t be achieved. The aim of this work was to develop an effective method for biologically active molecules incorporation onto the surface of CаP materials, and to study the dynamics of its release. Octacalcium phosphate (OCP), β-tricalcium phosphate (β-TCP) and β-tricalcium phosphate with biomimetic calcium phosphate layer (β-TCPmod.) were used as ceramic bioactive carriers. Bovine serum albumin (BSA) was used as a model compounds. BSA incorporation on the ceramics surface was performed by biomimetic co-precipitation from several buffer solutions containing the incorporated compound. The efficiency of biomolecules incorporation was evaluated by measuring BSA concentrations in solutions before and after materials incubation. The release of the incorporated molecules from the materials was investigated for 6 days. The structure and composition of the obtained materials were studied by application of XRD, FTIR, SEM, BET methods. It was shown that the OCP specific surface (surface area, (SBET)) was almost in 12 times higher than SBET of β-TCP. By using biomimetic approach the increase of β-TCP surface area in 1.6 times was achieved; this enhanced protein incorporation more than 3 times. The BSA biomimetic co-precipitation together with CaP on the OCP surface proved to be more effective than its adsorption from salt free solutions. The study of BSA release revealed that only 45% of loaded albumin released during 6 days of observation. Therefore, the effective method of CaP functionalization was developed. Based on biomolecules incorporation by biomimetic co-precipitation from CaP solutions, it provided a low rate of its release.
{"title":"The Functionalization of Calcium Phosphate Materials of Protein-based Biologically Active Molecules","authors":"E. A. Kuvshinova, N. V. Petrakova, N. Sergeeva, V. Kirsanova, I. Sviridova, A. Teterina, V. Komlev, A. Kaprin","doi":"10.18097/bmcrm00096","DOIUrl":"https://doi.org/10.18097/bmcrm00096","url":null,"abstract":"Recent approaches to the calcium phosphate (CaP) materials functionalization with drugs and biomolecules have been actively developed for bone defect reconstruction. However, the current techniques are low efficient in context of drug incorporation and non-controlled release from the materials. Eventually, continuous therapeutic effect in bone defect area couldn’t be achieved. The aim of this work was to develop an effective method for biologically active molecules incorporation onto the surface of CаP materials, and to study the dynamics of its release. Octacalcium phosphate (OCP), β-tricalcium phosphate (β-TCP) and β-tricalcium phosphate with biomimetic calcium phosphate layer (β-TCPmod.) were used as ceramic bioactive carriers. Bovine serum albumin (BSA) was used as a model compounds. BSA incorporation on the ceramics surface was performed by biomimetic co-precipitation from several buffer solutions containing the incorporated compound. The efficiency of biomolecules incorporation was evaluated by measuring BSA concentrations in solutions before and after materials incubation. The release of the incorporated molecules from the materials was investigated for 6 days. The structure and composition of the obtained materials were studied by application of XRD, FTIR, SEM, BET methods. It was shown that the OCP specific surface (surface area, (SBET)) was almost in 12 times higher than SBET of β-TCP. By using biomimetic approach the increase of β-TCP surface area in 1.6 times was achieved; this enhanced protein incorporation more than 3 times. The BSA biomimetic co-precipitation together with CaP on the OCP surface proved to be more effective than its adsorption from salt free solutions. The study of BSA release revealed that only 45% of loaded albumin released during 6 days of observation. Therefore, the effective method of CaP functionalization was developed. Based on biomolecules incorporation by biomimetic co-precipitation from CaP solutions, it provided a low rate of its release.","PeriodicalId":286037,"journal":{"name":"Biomedical Chemistry: Research and Methods","volume":"23 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121280134","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}
The goal of study was the determination of the ionization constants for the oximes – cholinesterases reactivators in aqueous solutions at different temperatures. The wavelengths of absorption maxima of the protonated and deprotonated oxime groups, the molar extinction coefficients of the various oximes species, and the ionization constants for the oxime cholinesterases reactivators (isonitrosin, pralidoxime, dipyroxime, toxogonin, methoxime, carboxime and asoxime) were obtained using spectrophotometric data (wavelength 190 to 450 nm) in solutions (pH 5 – 12) at 20°C, 25°C and 37°C. The proportion of nucleophilic forms involved in the oxime-induced reactivation of phosphorylated cholinesterases was shown to be is positively dependent on the incubation medium pH value and temperature. A hypothesis that the temperature affects the oximes ability to reactivate phosphorylated cholinesterases has been proposed.
{"title":"Spectrophotometric Determination of the Ionization Constants for the Oximes – Cholinesterases Reactivators at Different Temperatures","authors":"T. V. Schäfer, A. Tyaptin, T. B. Pechurina","doi":"10.18097/bmcrm00097","DOIUrl":"https://doi.org/10.18097/bmcrm00097","url":null,"abstract":"The goal of study was the determination of the ionization constants for the oximes – cholinesterases reactivators in aqueous solutions at different temperatures. The wavelengths of absorption maxima of the protonated and deprotonated oxime groups, the molar extinction coefficients of the various oximes species, and the ionization constants for the oxime cholinesterases reactivators (isonitrosin, pralidoxime, dipyroxime, toxogonin, methoxime, carboxime and asoxime) were obtained using spectrophotometric data (wavelength 190 to 450 nm) in solutions (pH 5 – 12) at 20°C, 25°C and 37°C. The proportion of nucleophilic forms involved in the oxime-induced reactivation of phosphorylated cholinesterases was shown to be is positively dependent on the incubation medium pH value and temperature. A hypothesis that the temperature affects the oximes ability to reactivate phosphorylated cholinesterases has been proposed.","PeriodicalId":286037,"journal":{"name":"Biomedical Chemistry: Research and Methods","volume":"50 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131923852","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}
V. Y. Grigorev, K. Shcherbakov, D. E. Polianczyk, А.N. Razdolsky, A. Veselovsky, V. Grigoriev, A. Yarkov, О.А. Raevsky
29 conjugates of methylene blue and four chemical structures, including derivatives of carbazole, tetrahydrocarbazole, substituted indoles and γ-carboline, combined with a 1-oxopropylene spacer have been studied as channel blockers of the NMDA receptor (binding site of MK-801) by using four QSAR methods (multiple linear regression, random forest, support vector machine, Gaussian process) and molecular docking. QSAR models have satisfactory characteristics. The analysis of regression models at the statistical level revealed an important role of the hydrogen bond in the complex formation. This was also confirmed by the study of modeled by docking complexes. It was found that the increase in the inhibitory activity of the part of compounds could be attributed to appearance of additional H bonds between the ligands and the receptor.
{"title":"Investigation of NMDA Receptor Channel Blockers in a Series of Methylene Blue Conjugates Using QSAR and Molecular Modeling","authors":"V. Y. Grigorev, K. Shcherbakov, D. E. Polianczyk, А.N. Razdolsky, A. Veselovsky, V. Grigoriev, A. Yarkov, О.А. Raevsky","doi":"10.18097/BMCRM00091","DOIUrl":"https://doi.org/10.18097/BMCRM00091","url":null,"abstract":"29 conjugates of methylene blue and four chemical structures, including derivatives of carbazole, tetrahydrocarbazole, substituted indoles and γ-carboline, combined with a 1-oxopropylene spacer have been studied as channel blockers of the NMDA receptor (binding site of MK-801) by using four QSAR methods (multiple linear regression, random forest, support vector machine, Gaussian process) and molecular docking. QSAR models have satisfactory characteristics. The analysis of regression models at the statistical level revealed an important role of the hydrogen bond in the complex formation. This was also confirmed by the study of modeled by docking complexes. It was found that the increase in the inhibitory activity of the part of compounds could be attributed to appearance of additional H bonds between the ligands and the receptor.","PeriodicalId":286037,"journal":{"name":"Biomedical Chemistry: Research and Methods","volume":"270 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116912718","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}
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