蛋氨酸衍生物缓蚀剂的合成与性能研究

以蛋氨酸为基础通过酰胺化反应合成一种新型的蛋氨酸衍生物缓蚀剂,应用极化曲线、电化学阻抗谱图研究蛋氨酸及其衍生物在3(wt)%Na Cl溶液中对N80碳钢的缓蚀作用,利用SEM观察添加缓蚀剂过后钢片表面的腐蚀形貌,并从分子结构上探讨了缓蚀剂在碳钢表面的作用机理。结果表明,蛋氨酸及其衍生物都属于阳极型缓蚀剂,且缓蚀率随着添加浓度增加而增加,添加250mg/L蛋氨酸衍生物在3(wt)%Na Cl溶液中对N80碳钢的缓蚀率达到86.94%。相同浓度条件下蛋氨酸衍生物的缓蚀率要高于蛋氨酸,其原因是蛋氨酸衍生物分子结构中增加了吸附位点和疏水长链。     

A label-free and sensitive fluorescent assay for one step detection of protein kinase activity and inhibition

In this paper, a label-free, highly sensitive and simple assay for one step detection of protein kinase (PKA) activity and inhibition that avoids the fluorescent dye process has been established. The detection was based on the fluorescence (FL) quenching of peptide-Ag nanoclusters (Ag NCs) caused by antibody modified Au nanoparticles (anti-Au NPs) via fluorescence resonance energy transfer (FRET). With PKA and adenosine 5′-triphosphate (ATP) introduced, the substrate peptide of Ag NCs could react with PKA via targeted phosphorylation, and followed by the linking interactions between peptide-Ag NCs and anti-Au NPs. According to the fluorescence quenching of Ag NCs, the activity of protein kinase can be facilely monitored in the range of 0.1–2000 mU/μL with high sensitivity. The detection limit for PKA is 0.039 mU/μL. We further explored the inhibitory effect of H-89 for protein kinase activity. The developed method was also applied to the investigation of drug-induced PKA activation in HeLa cells, which provides a promising means for screening of kinase-related drugs and the clinical diagnosis of disease.     

Mechanism of inhibition of human secretory phospholipase A2 by flavonoids: rationale for lead design

The human secretory phospholipase A2 group IIA (PLA2-IIA) is a lipolytic enzyme. Its inhibition leads to a decrease in eicosanoids levels and, thereby, to reduced inflammation. Therefore, PLA2-IIA is of high pharmacological interest in treatment of chronic diseases such as asthma and rheumatoid arthritis. Quercetin and naringenin, amongst other flavonoids, are known for their anti-inflammatory activity by modulation of enzymes of the arachidonic acid cascade. However, the mechanism by which flavonoids inhibit Phospholipase A2 (PLA2) remained unclear so far. Flavonoids are widely produced in plant tissues and, thereby, suitable targets for pharmaceutical extractions and chemical syntheses. Our work focuses on understanding the binding modes of flavonoids to PLA2, their inhibition mechanism and the rationale to modify them to obtain potent and specific inhibitors. Our computational and experimental studies focused on a set of 24 compounds including natural flavonoids and naringenin-based derivatives. Experimental results on PLA2-inhibition showed good inhibitory activity for quercetin, kaempferol, and galangin, but relatively poor for naringenin. Several naringenin derivatives were synthesized and tested for affinity and inhibitory activity improvement. 6-(1,1-dimethylallyl)naringenin revealed comparable PLA2 inhibition to quercetin-like compounds. We characterized the binding mode of these compounds and the determinants for their affinity, selectivity, and inhibitory potency. Based on our results, we suggest C(6) as the most promising position of the flavonoid scaffold to introduce chemical modifications to improve affinity, selectivity, and inhibition of PLA2-IIA by flavonoids.     

菜豆凝集素抑制剂的设计与凝血活性

针对菜豆凝集素二聚体复合物的结构特征,利用计算机辅助药物设计的方法设计抑制剂以破坏复合物结构;进一步采用标准的Fomc保护氨基酸NT氨基的固相法合成纯化了小肽抑制剂.体外兔血红细胞凝集实验结果表明,该小肽对菜豆凝集素的凝血能力有一定的抑制效果.该方法为植物凝集素凝血研究及菜豆相关的食品安全问题提供了一个新思路.     

Development of gold nanoparticle based colorimetric method for quantitatively studying the inhibitors of Cu/Zn induced β-amyloid peptide assembly

In this paper, a kind of gold nanoparticle (GNP)-based colorimetric assay has been developed for studying the reversible interaction of β-amyloid peptide (Aβ) with Cu²⁺ and Zn²⁺, and quantitatively analyzing four inhibitors (i.e., EDTA, EGTA, histidine and clioquinol) of Cu²⁺/Zn²⁺ induced Aβ assembly. The inhibition efficiencies (e.g., half maximal inhibitory concentration, IC₅₀ value) of these inhibitors could be measured in this work. As far as we know, these IC₅₀ values were reported at the first time. In this assay, the streptavidin conjugated GNPs (SA-GNPs) were employed as indicators to monitor the Cu²⁺/Zn²⁺ induced aggregating/disaggregating behaviors of biotin modified β-amyloid 1–16 peptides (Aβ_1–16(biotin)). Because of high affinity of streptavidin (SA) with biotin, the aggregating/disaggregating of Aβ_1–16(biotin) results in the significant color change of SA-GNPs. Furthermore, we demonstrate that the assay can be used as an effective tool for designing anti-dementia drugs through quantitative analysis of the interactions of four representative inhibitors with Cu²⁺/Zn²⁺ induced Aβ assembly.     

Synthesis,molecular docking,and inhibitory activity of a Ni Schiff-base complex against urease

A Ni(II) Schiff-base complex, Ni(C₁₄H₁₀NOBr₂)₂, was synthesized and structurally characterized by single-crystal X-ray analysis. Its inhibitory activity against Helicobacter pylori urease was evaluated in vitro and showed strong inhibitory activity against H. pylori urease compared with acetohydroxamic acid (IC₅₀ = 42.12 µmol L^?1), which is a positive reference. A docking analysis using the autodock 4.0 program could explain the inhibitory activity of the complex against urease.     

A novel optical nanoprobe for trypsin detection and inhibitor screening based on Mn-doped ZnSe quantum dots

In this paper, a novel optical nanoprobe (Mn:ZnSe d-dots-Arg₆) for trypsin detection and its inhibitor screening has been constructed successfully based on the fluorescence quenching and recovery of Mn:ZnSe d-dots. Mn:ZnSe d-dots would aggregate in the presence of positively charged Arg₆ (six arginine residues) due to electrostatic interactions that result in the fluorescence quenching. Arg₆ can be hydrolyzed into small fragments in the presence of trypsin, and accordingly, the aggregation of Mn:ZnSe d-dots can be prohibited, which lead to the fluorescence recovery. Experimental results show that the recovery in fluorescence intensity is linearly proportional to the concentration of trypsin within the range of 0.1–12.0 μg mL⁻¹ with a detection limit of 40 ng mL⁻¹ under the optimized experimental conditions. We also prove the feasibility of fluorescence recovery of Mn:ZnSe d-dots for trypsin detection through the resonance light scattering (RLS) technique. Additionally, the optical nanoprobe can be employed for screening the inhibitors of trypsin. The optical nanoprobe was successfully applied for the determination of trypsin in human serum and urine samples with good accuracy and satisfactory recovery.     

N—烷氧甲基取代丙烯酰胺的制备

Ｎ—烷氧甲基取代丙烯酰胺的制备张志成，吴国忠，王胜，徐相凌（中国科学技术大学应用化学系合肥２３００２６）关键词丙烯酰胺，阻聚剂，醚化Ｎ－烷氧甲基取代丙烯酰胺的结构通式为：ＣＨ＿２＝Ｃ－ＣＯＮＨＣＨ＿２ＯＲ＿２Ｒ＿１＝Ｈ．ＣＨ＿３；Ｒ＿２＝Ｈ，Ｍｅ，Ｅ...     

新型京尼平衍生物的合成、表征及抗糖尿病活性

为了寻找新型的抗糖尿病分子,从京尼平出发,经过甲基化（苄基化）、甲磺酰基取代、叠氮基取代和还原等4步反应得到含有活泼胺基的2个母核化合物. 这2个母核化合物与不同的酰氯反应,共得到13个新的京尼平衍生物,总收率41%~63%,其结构经核磁共振、质谱和元素分析确认. 活性测试结果表明,所有目标化合物在10 mmol/L 浓度下都有一定的抗糖尿病活性,其中化合物10f对二肽基肽酶4（DPP Ⅳ）的抑制率达31.2%.