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61.
Fataneh Jafari Setareh Samadi Amin Nowroozi Komail Sadrjavadi Sajad Moradi Mohammad Reza Ashrafi-Kooshk 《Journal of biomolecular structure & dynamics》2018,36(6):1490-1510
In the present research, the binding properties of diazinon (DZN), as an organophosphorus herbicide, to human serum albumin (HSA) were investigated using combination of spectroscopic, electrochemistry, and molecular modeling techniques. Changes in the UV–Vis and FT-IR spectra were observed upon ligand binding along with a significant degree of tryptophan fluorescence quenching on complex formation. The obtained results from spectroscopic and electrochemistry experiments along with the computational studies suggest that DZN binds to residues located in subdomains IIA of HSA with binding constant about 1410.9 M?1 at 300 K. From the thermodynamic parameters calculated according to the van’t Hoff equation, the enthalpy change ΔH° and entropy change ΔS° were found to be ?16.695 and 0.116 KJ/mol K, respectively. The primary binding pattern is determined by hydrophobic interaction and hydrogen binding occurring in so-called site I of HSA. DZN could slightly alter the secondary structure of HSA. All of experimental results are supported by computational techniques such as docking and molecular dynamics simulation using a HSA crystal model. 相似文献
62.
Molecular interactions of thymol with bovine serum albumin: Spectroscopic and molecular docking studies 下载免费PDF全文
Leila Roufegarinejad Ali Jahanban‐Esfahlan Sanaz Sajed‐Amin Vahid Panahi‐Azar Mahnaz Tabibiazar 《Journal of molecular recognition : JMR》2018,31(7)
Thymol is the main monoterpene phenol present in the essential oils which is used in the food industry as flavoring and preservative agent. In this study, the interaction of thymol with the concentration range of 1 to 6 μM and bovine serum albumin (BSA) at fixed concentration of 1 μM was investigated by fluorescence, UV‐vis, and molecular docking methods under physiological‐like condition. Fluorescence experiments were performed at 5 different temperatures, and the results showed that the fluorescence quenching of BSA by thymol was because of a static quenching mechanism. The obtained binding parameters, K, were in the order of 104 M?1, and the binding number, n, was approximately equal to unity indicating that there is 1 binding site for thymol on BSA. Calculated thermodynamic parameters for enthalpy (ΔH), entropy (ΔS), and Gibb's free energy (ΔG) showed that the reaction was spontaneous and hydrophobic interactions were the main forces in the binding of thymol to BSA. The results of UV‐vis spectroscopy and Arrhenius' theory showed the complex formation in the interaction of thymol and BSA. Negligible conformational changes in BSA by thymol were observed in fluorescence experiments, and the same results were also obtained from UV‐vis studies. Results of molecular docking indicated that the subdomain IA of BSA was the binding site for thymol. 相似文献
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64.
Johnson AA Santos W Pais GC Marchand C Amin R Burke TR Verdine G Pommier Y 《The Journal of biological chemistry》2006,281(1):461-467
Integration is essential for retroviral replication and gene therapy using retroviral vectors. Human immunodeficiency virus, type 1 (HIV-1), integrase specifically recognizes the terminal sequences of each long terminal repeat (LTR) and cleaves the 3'-end terminal dinucleotide 5'-GT. The exposed 3'-hydroxyl is then positioned for nucleophilic attack and subsequent strand transfer into another DNA duplex (target or chromosomal DNA). We report that both the terminal cytosine at the protruding 5'-end of the long terminal repeats (5'-C) and the integrase residue Gln-148 are critical for strand transfer. Proximity of the 5'-C and Gln-148 was demonstrated by disulfide cross-linking. Cross-linking is inhibited by the inhibitor 5CITEP 1-(5-chloroindol-3-yl)-3-hydroxy-3-(2H-tetrazol-5-yl)-propenone. We propose that strand transfer requires a conformational change of the integrase-viral (donor) DNA complex with formation of an H-bond between the N-3 of the 5'-C and the amine group of Gln-148. These findings have implications for the molecular mechanisms coupling 3'-processing and strand transfer as well as for the molecular pharmacology of integrase inhibitors. 相似文献
65.
This study communicates the molecular design, preparation, and biological application of novel symmetric amphiphilic polycationic dendritic poly(L-lysine)-b-poly(L-lactide)-b-dendritic poly(L-lysine) D2-LLA15-D2 bearing two two-generation poly(L-lysine) PLL dendrons D2 and a central hydrophobic biodegradable poly(L-lactide) block LLA15. First, an amino-protected precursor of L1-OH was designed and synthesized and was further employed to prepare L1-LLA15 with an organic 4-(dimethylamino)-pyridine-mediated living-ring-opening polymerization of l-lactide. Subsequently, the hydroxy end-capped L1-LLA15 was coupled to synthesize a new triblock L1-LLA15-L1 with two one-generation amino-protected PLL dendrons L1. Furthermore, with a repeated trifluoroacetic-acid-mediated amino deprotection-protection cycle, new amphiphilic triblock D2-LLA15-D2 was successfully prepared. By means of NMR, mass spectrometry, and gel permeation chromatography, these synthetic precursors and final amphiphilic product were characterized to bear well-defined triblock structures. In addition, this synthesized amphiphilic triblock polycationic macromolecule was applied as a new polycationic plasmid DNA carrier, and its DNA binding affinity was examined via an agarose electrophoresis and a fluorescence titration assay along with two important references of hydrophilic dendritic D2-HEX-D2 and double-hydrophilic D2-PEG-4K-D2 bearing the same two D2 dendrons; much enhanced DNA binding affinity was interestingly revealed for the new amphiphilic structural D2-LLA15-D2. Moreover, the assembled polyplex microparticles of plasmid DNA/polycationic carrier were further analyzed by dynamic light scattering and transmission electron microscopy, indicating their averaged nanoparticle size around 150-200 nm. As for the cytotoxicity of the new D2-LLA15-D2, MTT assays were conducted with a human hepatocellular carcinoma cell line (SMMC-7721), indicating a very low cytotoxicity as compared with commercial linear PLL-23K and PEI-2K, and a DNase I degradation of the assembled polyplex particles was also done in the HBS buffer solution to evaluate their stabilities. Finally, employing the new amphiphilic D2-LLA15-D2 as gene carrier, in vitro gene transfection experiments were conducted with the SMMC-7721 cell line, indicating a transfection efficiency increase of at least 10 times higher than that of the naked plasmid DNA under a N/P charge ratio of 10. Therefore, these interesting results may provide a new possible way to construct efficient polycationic macromolecular gene carriers with low toxicity and less expensive low-generation PLL dendrons. 相似文献
66.
BACKGROUND/AIMS: Turner's syndrome (TS) is associated with increased insulin resistance and adiposity, which might be associated with type 2 diabetes in later life. We aimed to determine whether the defect in insulin sensitivity is a primary intrinsic defect in TS or dependent on variation in body composition. METHODS: Sixteen women with TS not on growth hormone replacement but receiving oestrogen replacement therapy [age (mean +/- SD): 30.2 +/- 8.5 years; height-corrected fat-free mass: 26.1 +/- 3.1 kg/height] and a control group of 16 normal healthy women (age: 30.1 +/- 8.2 years; height-corrected fat-free mass: 25.9 +/- 2.4 kg/height) were studied. Fasting blood samples were obtained for measurement of glucose, insulin, IGF-I, IGFBP-1, IGFBP-3 and lipid levels. The hyperinsulinaemic euglycaemic clamp was performed to assess peripheral insulin sensitivity (M value), and the Homeostasis Model Assessment (HOMA-S) was used to estimate fasting insulin sensitivity. Body composition was assessed using a dual-energy X-ray absorptiometry scan. RESULTS: Fasting insulin sensitivity (HOMA-S 103.2 +/- 78.6 vs. 193.9 +/- 93.5, p = 0.006) was lower in TS subjects compared to controls as was whole-body insulin sensitivity (M value 2.9 +/- 1.9 vs. 5.5 +/- 2.6 mg/kg/min, p = 0.003). In a multiple regression analysis the Turner karyotype was significantly related to insulin sensitivity (p = 0.008) independent of any differences in fat-free mass and percent whole-body fat mass. CONCLUSION: The increased insulin resistance in women with TS is independent of measures of body composition and may represent an intrinsic defect related to their chromosomal abnormality. 相似文献
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68.
明晰甘肃安西极旱荒漠国家级自然保护区珍稀濒危物种北山羊的分布格局,并阐释气候变化和人类活动对北山羊的影响,对今后北山羊生境管理和物种保护具有重要意义。基于北山羊实测分布点记录和环境变量数据,结合MaxEnt模型和ArcGIS空间分析功能,利用CMIP6的8个气候模式均值预测中度发展路径(SSP2-4.5)下,基准期(1970-2000年)和未来气候(2041-2060年、2081-2100年)变化情景下,甘肃安西极旱荒漠国家级自然保护区北山羊的潜在适生区分布范围及变化,并综合贡献率和置换重要性值对北山羊生境选择关键环境因子进行了分析。研究结果表明:(1) MaxEnt模型的预测精度较高,三种气候条件下ROC曲线下面积(AUC,Area Under Curve)>0.97,且真实技巧统计(TSS,True Skill Statistic)>0.90,模拟结果可靠。(2)影响北山羊生境选择的主要环境因子为气候条件(降水量季节性变异系数和等温性)、海拔和人为干扰(距泉和居名点距离)。水是保护区北山羊生存的最基本要素,气候条件共同控制北山羊生境条件。此外,北山羊习性决定其生境宜选择高海拔和远离人类活动影响地区。(3)基准期保护区北山羊主要分布在北片和南片高海拔山区,面积365.77 km2(占整个保护区的4.31%),北山羊适生区面积北片>南片、中高等适生区主要位于保护区北片。(4) CMIP6未来气候变化情景下,随着保护区生态环境改善和濒危物种保护措施的实施,北山羊潜在适生区面积呈增加趋势,但是受北山羊近亲繁殖的影响,整体上北山羊数量和适生区面积增加并不显著且有向南部及高海拔地区转移趋势。 相似文献
69.
Saeed Mohammadian Haftcheshmeh Parvin Zamani Mohammad Mashreghi Amin Reza Nikpoor Jalil Tavakkol-Afshari Mahmoud Reza Jaafari 《Biotechnology progress》2021,37(2):e3095
LAG3-Ig as an immune adjuvant has elicited potent anti-tumor immune responses in several preclinical and clinical studies, but the full potential immunostimulatory of LAG3-Ig has yet to be achieved. We hypothesized that by anchoring LAG3-Ig to the surface of liposomes, the adjuvant activity of LAG3-Ig could be improved. We also investigated the immunotherapy by co-delivery of liposome-coupled LAG3-Ig and P5 tumor antigen in mice model of TUBO breast cancer. We prepared and characterized novel PEGylated liposomes bearing surface conjugated LAG3-Ig and P5. Consistent with our hypothesis, liposomes-conjugated LAG3-Ig via multivalent binding to MHC class II molecules exerted immunostimulatory of LAG3-Ig and markedly induced maturation of dendritic cells more efficiently than free LAG3-Ig. LAG3-Ig-P5-immunoliposomes effectively elicited protective anti-tumor responses more than locally injected soluble LAG3-Ig + P5. The higher percentage of CD4+ and CD8+ T cells in the spleen and more rapid and pronounced infiltration of these effector cells into the site of the tumor were seen following immunoliposome therapy. Finally, anti-tumor immunity induced by LAG3-Ig-P5-immunoliposomes translated into the more tumor regression and prolonged survival of treated mice, compared to soluble immunotherapy. Taken together, our findings suggest that LAG3-Ig-P5-immunoliposomes can be considered as a valuable candidate for developing a liposome-based therapeutic cancer vaccine in treating HER2/ neu+ breast cancer patients. 相似文献
70.
Prithwiraj De Anita G. Amin Danara Flores Anne Simpson Karen Dobos Delphi Chatterjee 《The Journal of biological chemistry》2021,297(5)
In Mycobacterium tuberculosis (Mtb), surface-exposed Lipoarabinomannan (LAM) is a key determinant of immunogenicity, yet its intrinsic heterogeneity confounds typical structure–function analysis. Recently, LAM gained a strong foothold as a validated marker for active tuberculosis (TB) infection and has shown great potential in new diagnostic efforts. However, no efforts have yet been made to model or evaluate the impact of mixed polyclonal Mtb infections (infection with multiple strains) on TB diagnostic procedures other than antibiotic susceptibility testing. Here, we selected three TB clinical isolates (HN878, EAI, and IO) and purified LAM from these strains to present an integrated analytical approach of one-dimensional and two-dimensional Nuclear Magnetic Resonance (NMR) spectroscopy, as well as enzymatic digestion and site-specific mass spectrometry (MS) to probe LAM structure and behavior at multiple levels. Overall, we found that the glycan was similar in all LAM preparations, albeit with subtle variations. Succinates, lactates, hydroxybutyrate, acetate, and the hallmark of Mtb LAM-methylthioxylose (MTX), adorned the nonreducing terminal arabinan of these LAM species. Newly identified acetoxy/hydroxybutyrate was present only in LAM from EAI and IO Mtb strains. Notably, detailed LC/MS-MS unambiguously showed that all acyl modifications and the lactyl ether in LAM are at the 3-OH position of the 2-linked arabinofuranose adjacent to the terminal β-arabinofuranose. Finally, after sequential enzymatic deglycosylation of LAM, the residual glycan that has ∼50% of α−arabinofuranose -(1→5) linked did not bind to monoclonal antibody CS35. These data clearly indicate the importance of the arabinan termini arrangements for the antigenicity of LAM. 相似文献