Russian Journal of Bioorganic Chemistry最新文献

筛选
英文 中文
Promising Directions for Regulating Signaling Pathways Involved in the Type 2 Diabetes Mellitus Development (A Review) 调节参与 2 型糖尿病发病的信号通路的可行方向(综述)
IF 1 4区 化学
Russian Journal of Bioorganic Chemistry Pub Date : 2024-08-05 DOI: 10.1134/s1068162024040137
N. A. Borozdina, I. A. Dyachenko, D. V. Popkova
{"title":"Promising Directions for Regulating Signaling Pathways Involved in the Type 2 Diabetes Mellitus Development (A Review)","authors":"N. A. Borozdina, I. A. Dyachenko, D. V. Popkova","doi":"10.1134/s1068162024040137","DOIUrl":"https://doi.org/10.1134/s1068162024040137","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Many studies confirm that substances of natural origin have a pronounced affinity for type 2 diabetes mellitus (T2DM) therapeutic targets. At the moment, there is growing interest in bioactive peptides, phytochemicals, and drugs from other natural sources as highly effective, safe and promising antidiabetic agents. Natural sources are a promising resource for regulating several pathological pathways in T2DM. The review describes ways to mitigate insulin resistance and tissue sensitivity to glucose through PTP1β (protein tyrosine phosphatase 1β), GLP-1R (glucagon-like peptide receptor), DPP-4 (dipeptidyl peptidase-4), AMPK (adenosine monophosphate activated protein kinase), MAPK (mitogen-activated protein kinase). The review includes ways to regulate obesity and oxidative stress development through CCN3 (nephroblastoma overexpressed gene), PPAR-γ (peroxisome proliferator-activated receptor γ), Nrf2 (nuclear factor erythroid-related factor 2), FFAR (free fatty acid receptors), 11β-HSD1 (11β-hydroxysteroid dehydrogenase). Moreover, the review details the regulation of hyperglycemia through alpha-amylase inhibitors, as well as regulation of glucose metabolism through GFAT (glutamine fructose6-phosphate aminotransferase), FOXO1 (forkhead box protein O1), GLUT4 (glucose transporter type 4), PGC-1α (receptor gamma coactivator 1α activating peroxisome proliferator). The review examines the use of natural sources, from which low-molecular-weight and peptide compounds are used as T2DM targets modulators.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In Vitro and In Silico Evaluation of 2-(1H-Benzo[d]imidazol-2-yl)-3-(4-(piperazin-1-yl)phenyl)propanenitrile as Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors 2-(1H-苯并[d]咪唑-2-基)-3-(4-(哌嗪-1-基)苯基)丙腈作为表皮生长因子受体酪氨酸激酶抑制剂的体外和硅学评估
IF 1 4区 化学
Russian Journal of Bioorganic Chemistry Pub Date : 2024-08-05 DOI: 10.1134/s1068162024040174
K. Sarita, N. Kumar, A. Agrawal, S. N. Mali, S. Sharma
{"title":"In Vitro and In Silico Evaluation of 2-(1H-Benzo[d]imidazol-2-yl)-3-(4-(piperazin-1-yl)phenyl)propanenitrile as Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors","authors":"K. Sarita, N. Kumar, A. Agrawal, S. N. Mali, S. Sharma","doi":"10.1134/s1068162024040174","DOIUrl":"https://doi.org/10.1134/s1068162024040174","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p><b>Objective:</b> Advanced cancer treatment is based on targeted therapy, providing greater precision while mitigating common drug toxicity and resistance. Recently, protein kinases have gained prominence as valuable subjects for cancer therapy. <b>Methods:</b> To investigate the anticancer potential of benzimidazole analogues, various derivatives of 2-(1H-benzimidazol-2-yl)-3-(4-(4-substituted-piperazin-1-yl)phenyl)propane nitriles (<b>IIa–IIj</b>) were synthesized. All the synthesized analogues were characterized through TLC, melting points, FT-IR, <sup>1</sup>H NMR, <sup>13</sup>C, and mass spectroscopy. The anticancer potential of synthesized analogues was determined through the sulforhodamine B (SRB) assay against lung carcinoma cell lines (A549) and % growth inhibition was determined using Dalton’s lymphoma ascites cells. A molecular docking study was performed against epidermal growth factor receptor tyrosine kinase (a selective target for inhibitors of cancer) to illustrate the binding modes of ligands in the EGFR target. <b>Results and Discussion:</b> In vitro cytotoxic studies revealed that derivatives (<b>IIh</b>) and (<b>IIa</b>) showed promising anticancer activity. <b>Conclusions:</b> It is concluded from <i>in vitro</i> and <i>in silico</i> studies that compound (<b>IIh</b>) showed significant a significant anticancer activity.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Design, Synthesis, and Antibacterial Evaluation of Novel Coumarin Based 1,2,3-Triazole Derivatives 新型香豆素基 1,2,3-三唑衍生物的设计、合成和抗菌评估
IF 1 4区 化学
Russian Journal of Bioorganic Chemistry Pub Date : 2024-08-05 DOI: 10.1134/s1068162024040198
J. Gogoi, B. Chetia, J. G. Handique, S. Saikia, P. Chetia
{"title":"Design, Synthesis, and Antibacterial Evaluation of Novel Coumarin Based 1,2,3-Triazole Derivatives","authors":"J. Gogoi, B. Chetia, J. G. Handique, S. Saikia, P. Chetia","doi":"10.1134/s1068162024040198","DOIUrl":"https://doi.org/10.1134/s1068162024040198","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p><b>Objective:</b> Coumarin and triazole moiety itself is well known to have wide range of biological properties including antibacterial activities. In this work, we have designed and synthesized a series of novel coumarin based 1,2,3-triazole derivatives (<b>VIa–VIi</b>) and reported them as potent antibacterial agent. <b>Methods:</b> All the synthesized compounds were characterized using different spectroscopic methods. The antibacterial properties of our designed compounds were evaluated by calculating the minimum inhibitory concentration (MIC) against the bacterial panel <i>Escherichia coli</i> (<i>E. coli</i>), <i>Pseudomonas aeruginosa</i> (<i>P. aeruginosa</i>), <i>Staphylococcus aureus</i> (<i>S. aureus</i>), and <i>Bacillus subtilis</i> (<i>B. subtilis</i>). Further, molecular docking analysis were also performed in order to determine the binding modes and binding energies of the potent hybrids. The <i>in silico</i> method has been used for determining the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of (<b>VIc</b>), (<b>VId</b>), (<b>VIg</b>), and (<b>VIh</b>). <b>Results and Discussion:</b> Here, we have successfully synthesized nine novel coumarin based 1,2,3-triazole conjugates using cycloaddition reaction. All the compounds were found to be active against the tested bacterial panel with MIC values ranging from 12.5 to 200 µg/mL. Among them four compounds (<b>VIc</b>), (<b>VId</b>), (<b>VIg</b>), and (<b>VIh</b>) showed broad spectrum of antibacterial activities. Out of these four, the compound (<b>VIh</b>) showed excellent inhibitory action against <i>B. subtilis</i> and compounds (<b>VIg</b>), (<b>VIh</b>) showed great inhibition activity against <i>S. aureus</i> in comparison to the standard drug streptomycin. The molecular docking study also revealed the binding capabilities of our designed compounds with the different active site of the protein (PDB ID: 4OZ5) extracted from <i>B. subtilis</i> with great affinity. <b>Conclusions:</b> From the calculated MIC values, we can conclude that our compounds can act as a potent antibacterial agent against the tested bacteria panel. The <i>in silico</i> results also help to understand the mode of inhibitory action and justify the potential of the synthesized compounds as excellent antibacterial agent.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141968939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Optimized Protocol for Production and Extraction of Colanic Acid from E. coli Culture 从大肠杆菌培养物中生产和提取高良酸的优化方案
IF 1 4区 化学
Russian Journal of Bioorganic Chemistry Pub Date : 2024-08-05 DOI: 10.1134/s1068162024040344
S. A. Tsvetikova, E. I. Koshel
{"title":"Optimized Protocol for Production and Extraction of Colanic Acid from E. coli Culture","authors":"S. A. Tsvetikova, E. I. Koshel","doi":"10.1134/s1068162024040344","DOIUrl":"https://doi.org/10.1134/s1068162024040344","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p><b>Objective:</b> Colanic acid (CA) is a promising and actively studied polysaccharide, which geroprotective and stimulating properties have already been described in animal models. Different protocols are used to isolate and purify CA in research, some of which may result in contamination with proteins, DNA, and other polysaccharides. <b>Methods:</b> In order to effectively further investigate the biological properties of CA, we developed 5 protocols for CA isolation, differed in cultivation condition, protein precipitation, and polysaccharide precipitants. <b>Results and Discussion:</b> We found that the most suitable protocol for CA isolation includes protein removal with trichloroacetic acid and polysaccharide precipitation with ethanol (95%, 3 volumes). <b>Conclusions:</b> Such a simple protocol will serve to standardize CA studies and can be applied to obtain large volumes of polysaccharide.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Design, Synthesis, and Antimicrobial Evaluation of Quinolones Containing 1,2,3-Triazole Moieties: In Silico Docking Techniques 含 1,2,3-三唑分子的喹诺酮类药物的设计、合成和抗菌评估:硅学对接技术
IF 1 4区 化学
Russian Journal of Bioorganic Chemistry Pub Date : 2024-08-05 DOI: 10.1134/s1068162024040277
G. Venkanna, A. Tejeswara Rao, K. Shiva Kumar, M. S. N. A. Prasad, C. Kalyani, G. Shravan Kumar, V. Srinivas
{"title":"Design, Synthesis, and Antimicrobial Evaluation of Quinolones Containing 1,2,3-Triazole Moieties: In Silico Docking Techniques","authors":"G. Venkanna, A. Tejeswara Rao, K. Shiva Kumar, M. S. N. A. Prasad, C. Kalyani, G. Shravan Kumar, V. Srinivas","doi":"10.1134/s1068162024040277","DOIUrl":"https://doi.org/10.1134/s1068162024040277","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p><b>Objective:</b> We have been studying the synthesis and biological activity of compounds that simultaneously comprise different heterocycles, like 1,2,3-triazoles and fused 2-quinolones, as part of our ongoing research in organic and medicinal chemistry. <b>Methods:</b> Using 6-methoxy-1-methyl-4-(prop-2-yn-1-yloxy)quinolin-2(1<i>H</i>)-one and various aryl azides, we developed and synthesized a number of novel quinolones linked 1,2,3-triazoles. The structures of the newly synthesized derivatives are characterized from IR, <sup>1</sup>H NMR, <sup>13</sup>C NMR, and mass analysis. The prepared derivatives were screened their <i>in vitro</i> antibacterial activity against <i>S. Epidermidis</i>,<i> S. aureus</i>,<i> S. Pneumonia</i>,<i> P. Aeruginosa</i> and antifungal activity against <i>A. niger</i> and <i>C. albicans.</i> <b>Results and Discussions:</b> Among all the synthesized compounds, 6-methoxy-1-methyl-4-((1-(pyridin-3-yl)-1<i>H</i>-1,2,3-triazol-4-yl)methoxy)quinolin-2(1<i>H</i>)-one have shown potent antibacterial activity against <i>S. Epidermidis</i>,<i> S. aureus</i>,<i> and S. Pneumonia</i> as compared to standard Moxifloxacin with MIC values 2.38 ± 0.01, 3.32 ± 0.04, and 2.52 ± 0.01 µg/mL. Similarly, antifungal activity of newly synthesized derivatives same compound has shown more potent activity against <i>A. niger</i> and<i> C. albicans</i> fungal strains with MIC values 2.67 ± 0.01 and 2.70 ± 0.01 µg/mL. <i>In silico</i> molecular docking results of more potent compounds were shown comparable binding energies. Finally, the <i>in silico</i> pharmacokinetic profile of all the synthesized derivatives were estimated using SwissADME and pkCSM, where all some of the compounds followed Lipinski, Veber, Egan, and Muegge rules without deviation. <b>Conclusions:</b> The focus of this research is on recent advances in drug design and development, as well as quinolone-triazole derivatives and how they work on antibacterial and antifungal sites of action.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ultrafast Photochemical Reaction of Exiguobacterium sibiricum Rhodopsin (ESR) at Alkaline pH 西西伯利亚外分支杆菌(ESR)在碱性 pH 下的超快光化学反应
IF 1 4区 化学
Russian Journal of Bioorganic Chemistry Pub Date : 2024-08-05 DOI: 10.1134/s1068162024040058
O. A. Smitienko, T. B. Feldman, L. E. Petrovskaya, E. A. Kryukova, I. V. Shelaev, F. E. Gostev, D. A. Cherepanov, I. B. Kolchugina, D. A. Dolgikh, V. A. Nadtochenko, M. P. Kirpichnikov, M. A. Ostrovsky
{"title":"Ultrafast Photochemical Reaction of Exiguobacterium sibiricum Rhodopsin (ESR) at Alkaline pH","authors":"O. A. Smitienko, T. B. Feldman, L. E. Petrovskaya, E. A. Kryukova, I. V. Shelaev, F. E. Gostev, D. A. Cherepanov, I. B. Kolchugina, D. A. Dolgikh, V. A. Nadtochenko, M. P. Kirpichnikov, M. A. Ostrovsky","doi":"10.1134/s1068162024040058","DOIUrl":"https://doi.org/10.1134/s1068162024040058","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p><b>Objective:</b> Rhodopsin from the eubacterium <i>Exiguobacterium sibiricum</i> (ESR) performs the lightdependent proton pumping function. The operation of ESR is based on the ultrafast photochemical reaction of isomerization of the retinal chromophore, which triggers dark processes closed in a photocycle. Many parameters of the photocycle are determined by the presence of a hydrogen bond between the primary counterion Asp85 and the chromophore. ESR in detergent micelles pumps protons most efficiently at pH &gt; 9, when such a bond is most probable. <b>Methods:</b> In the present study, the photochemical reaction of ESR at pH 9.5 was investigated by femtosecond laser absorption spectroscopy. <b>Results and Discussion:</b> It was shown that photoisomerization of the chromophore group occurs in 0.51 ps, with the contribution from the reactive excited state being ca. 80%. A comparison with the earlier obtained data for pH 7.4 showed that, at pH 9.5, the reaction proceeds much faster and more efficiently. <b>Conclusions:</b> The present results confirm the important role of the chromophore group counterion in the photoactivated processes of rhodopsins.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Design and Synthesis of Some New Benzimidazole-1,2,3-triazole-thiazolidine-2,4-dione Conjugates as Tubulin Polymerization Inhibitors 设计和合成一些新的苯并咪唑-1,2,3-三唑-噻唑烷-2,4-二酮共轭物作为微管蛋白聚合抑制剂
IF 1 4区 化学
Russian Journal of Bioorganic Chemistry Pub Date : 2024-08-05 DOI: 10.1134/s1068162024040307
B. Karthik, B. Ramakrishna, B. Ashok Kumar, T. Kranthi Kumar
{"title":"Design and Synthesis of Some New Benzimidazole-1,2,3-triazole-thiazolidine-2,4-dione Conjugates as Tubulin Polymerization Inhibitors","authors":"B. Karthik, B. Ramakrishna, B. Ashok Kumar, T. Kranthi Kumar","doi":"10.1134/s1068162024040307","DOIUrl":"https://doi.org/10.1134/s1068162024040307","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p><b>Objective:</b> It is worthy to note that the benzimidazole, thiazolidine-2,4-dione and 1,2,3-triazole pharmacophores have keen role in anticancer drug discovery. In order to overcome the limitations associated with reported antimitotic compounds, our group is first time combining these three pharmacophores and revealing their <i>in vitro</i> anticancer and anti-mitotic activities. <b>Methods:</b> As a part of our efforts on the development of novel anticancer agents, in this study, we concentrated on the synthesis of benzimidazole-thiazolidine-2,4-dione-1,2,3-triazoles (<b>VIIa­–VIIl</b>) via piperidine catalyzed Knoevenagel condensation and Cu(I) catalyzed azide-alkyne cycloaddition reactions as key approaches. Then, <i>in vitro</i> anticancer and tubulin polymerization inhibition (<b>VIIa–VIIl</b>) were studied via IC<sub>50</sub> values. Finally, docking interactions of three potent compounds (<b>VIIg</b>), (<b>VIIh</b>), and (<b>VIIk</b>) towards α,β-tubulin were studied using AutoDock tools. <b>Results and Discussion:</b> Three compounds namely (<b>VIIg</b>), (<b>VIIh</b>), and (<b>VIIk</b>) showed better results against A549, MCF-7, and HeLa human cancer cell lines than standard drug nocodazole. In addition, compounds (<b>VIIg</b>) and (<b>VIIh</b>) have shown greater inhibitory potency with IC<sub>50</sub> values 0.62 and 0.31 μM respectively than standard Combretastatin A-4 (CA-4) against tubulin polymerization. Finally, <i>in silico</i> molecular docking studies for the compounds (<b>VIIg</b>), (<b>VIIh</b>), and (<b>VIIk</b>) with α,β-tubulin showed that they have great binding interactions with the target protein and to be specific the compound (<b>VIIh</b>) displayed highest binding energy, i.e. –9.23 kcal/mol. <b>Conclusions:</b> We propose that the remarkable <i>in vitro</i> anticancer activity of compounds (<b>VIIg</b>), (<b>VIIh</b>), and (<b>VIIk</b>), would be due to their tubulin polymerization inhibition.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Photocleavable Guide RNA for Photocontrolled CRISPR/Cas9 System 用于光控 CRISPR/Cas9 系统的可光裂解引导 RNA
IF 1 4区 化学
Russian Journal of Bioorganic Chemistry Pub Date : 2024-08-05 DOI: 10.1134/s1068162024040046
E. A. Akhmetova, I. P. Vokhtantsev, M. I. Meschaninova, M. A. Vorobyeva, D. O. Zharkov, D. S. Novopashina
{"title":"Photocleavable Guide RNA for Photocontrolled CRISPR/Cas9 System","authors":"E. A. Akhmetova, I. P. Vokhtantsev, M. I. Meschaninova, M. A. Vorobyeva, D. O. Zharkov, D. S. Novopashina","doi":"10.1134/s1068162024040046","DOIUrl":"https://doi.org/10.1134/s1068162024040046","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p><b>Objective:</b> The development of CRISPR/Cas-based gene-editing systems having a higher efficacy and specificity, and capable of changing activity in response to light irradiation is an urgent problem. A promising approach to this problem is to modify CRISPR/Cas components, in particular guide RNA, by introducing photocleavable linkers. We developed an approach to the synthesis of photocleavable single guide RNA (sgRNA) for the CRISPR/Cas9 system containing linkers on the basis of 1-(2-nitrophenyl)-1,2-ethanediol. Such photomodified guide RNAs are cleaved under UV irradiation, thereby inactivating the CRISPR/Cas9 system. <b>Methods:</b> Automatic solid-phase phosphoramidate method was used for photomodified sgRNA synthesis. Model plasmid was used for designed system testing. <b>Results and Discussion:</b> We obtained three variants of photomodified sgRNA with different photolinker positions. Evidence was obtained showing that the sgRNA with the photolinker introduced in the protein Cas9 site of binding and hairpin formation is able to effectively guide Cas9 nuclease for target DNA cleavage before UV irradiation and lose its activity after irradiation. The conditions of controllable 40% cleavage of a model target DNA were chosen. <b>Conclusions:</b> The work presents the results of photocleavable sgRNA design and usage as a component of photoregulated CRISPR/Cas9 system. The developed approach makes possible specific inactivation of the CRISPR/Cas9 gene editing system in a specific time moment in a definite place. The photoregulation of the gene-editing system not only allows one to reduce undesirable off-target effects, but also forms the basis for genetic disease therapy.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
mKate2-K67R/R197H—Extra-Bright Red Fluorescent Biomarker of New Generation. X-Ray Structure and Molecular Dynamic Properties mKate2-K67R/R197H-新一代超亮红色荧光生物标记物。X 射线结构和分子动力学特性
IF 1 4区 化学
Russian Journal of Bioorganic Chemistry Pub Date : 2024-08-05 DOI: 10.1134/s1068162024040113
E. A. Goryacheva, A. V. Rossokhin, D. A. Ruchkin, A. M. Bogdanov, I. V. Artemyev, N. V. Pletneva, V. Z. Plenev
{"title":"mKate2-K67R/R197H—Extra-Bright Red Fluorescent Biomarker of New Generation. X-Ray Structure and Molecular Dynamic Properties","authors":"E. A. Goryacheva, A. V. Rossokhin, D. A. Ruchkin, A. M. Bogdanov, I. V. Artemyev, N. V. Pletneva, V. Z. Plenev","doi":"10.1134/s1068162024040113","DOIUrl":"https://doi.org/10.1134/s1068162024040113","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p><b>Objective:</b> Cell biology continuously shows the need for new fluorescent tags with advanced properties. The object of our current study is a new genetically encoded monomeric red fluorescent biomarker mKate2-K67R/R197H (λex/λem 579/603 mn), designed from commercial biomarker mKate2 by two R197H/K67R mutations. The mKate2 precursor, a far-red fluorescent protein, is nearly 3-fold brighter than the previously designed mKate. Compared with commercial mKate2, the double mutant mKate2-K67R/R197H (alternative names FusionRed2 and Diogenes) exhibits an additional ~1.6-fold increase in fluorescence brightness and represents the next generation of extra-bright red fluorescent probes offering novel possibilities for fluorescent imaging of proteins in living cells and animals. <b>Methods:</b> The paper presents the results of X-ray and molecular dynamics study of new bright biomarker mKate2-K67R/R197H. <b>Results and Discussion:</b> The three dimensional structure of new advanced red fluorescent biomarker mKate2-K67R/R197H has been studied by X-ray method at 1.5Å resolution supported by molecular dynamics (MD) study The principal structural fold of the protein is an 11-stranded β-barrel. The nearest chromophore environment (≤ 4 Å) comprises 18 tightly packed residues. <b>Conclusions:</b> The MD study showed that the brightness of mKate2-K67R/R197H and its mKate2 precursor correlates with the dipole moments of the amino acid environments of the chromophores. The higher the dipole moment, the higher the brightness of biomarker.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Architectonics of Ubiquitin Chains (A Review) 泛素链的结构学(综述)
IF 1 4区 化学
Russian Journal of Bioorganic Chemistry Pub Date : 2024-08-05 DOI: 10.1134/s106816202404006x
K. A. Ivanova, A. A. Belogurov, A. A. Kudriaeva
{"title":"Architectonics of Ubiquitin Chains (A Review)","authors":"K. A. Ivanova, A. A. Belogurov, A. A. Kudriaeva","doi":"10.1134/s106816202404006x","DOIUrl":"https://doi.org/10.1134/s106816202404006x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Ubiquitination, one of the most common posttranslational modifications of proteins, has a significant impact on their functions, such as stability, activity, and cellular localization. Disorders in the ubiquitination and deubiquitination processes are associated with various oncological and neurodegenerative diseases. The complexity of ubiquitin signaling, specifically monoubiquitination and polyubiquitination with different lengths and types of ubiquitin– ubiquitin linkages determines their versatility and ability to regulate hundreds of different cellular processes. Advanced biochemical, mass spectrometric, and computational studies are required for in-depth understanding of the mechanisms of assembly and disassembly, as well as detection of ubiquitin chains and their signal transmission. Recent scientific achievements make it possible to identify protein ubiquitination and the structure of ubiquitin chains, but there are a lot of issues in this area to be clarified. The present review provides a detailed analysis of the current understanding of the architectonics of ubiquitin chains.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":null,"pages":null},"PeriodicalIF":1.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信