丹酚酸A与人血清白蛋白的相互作用研究

研究药物和血浆中载体蛋白的相互作用对阐明药物在体内的转运、分布、代谢和药效等具有重要的意义。采用荧光光谱和紫外-可见吸收光谱法研究了不同温度下丹酚酸A(Sal A)与人血清白蛋白(HSA)的相互作用机理。研究结果表明,Sal A对HSA的内源荧光有明显的猝灭作用,猝灭过程为静态猝灭,并测定和计算得到不同温度下Sal A与HSA反应的结合常数、结合位点数。分析两者结合过程的热力学数据,表明Sal A和HSA的结合是一种自发的放热过程,且推测出Sal A与HSA之间的作用力为氢键和范德华力。     

提高柴油加氢精制催化剂活性的方法

依据过渡金属硫化物催化剂的活性相理论及加氢脱硫、脱芳反应的历程,综述了各种提高柴油加氢精制催化剂性能的方法--使用高加氢能力的活性组分、引入中等强度酸中心、减弱活性组分与载体间的相互作用以及提高活性组分的分散度;介绍了相关的国内外最新研究进展,指出研究开发高比表面积、中等酸性的介孔载体和既能提高活性组分分散度又不增强活性组分与载体间相互作用的新型催化剂制备方法是提高柴油加氢精制催化剂性能的主要途径.     

人血清白蛋白和菁染料的相互作用研究

研究菁染料分子DMSA与人血清白蛋白(HSA)之间的相互作用及DMSA对HSA构象的影响。采用荧光光谱研究菁染料DMSA与HSA的相互作用机制,通过计算结合常数和结合位点确定荧光猝灭类型;利用吸收光谱和同步荧光光谱探讨DMSA对HSA构象的影响。结果表明菁染料DMSA能猝灭HSA的内源性荧光,其猝灭机制为静态猝灭且DMSA与HSA之间具有很强的结合能力,结合常数Ka=7.73×106L·mol-1,结合位点n=1.59。此外,通过吸收光谱和同步荧光光谱探讨了DMSA对HSA构象的影响,DMSA的加入使HSA的结构变得疏松导致构象发生变化。     

乙炔氢氯化反应催化剂载体的研究进展

概述了近年来国内外乙炔氢氯化反应载体的研究现状包括金属/非金属氧化物、分子筛和炭材料等载体材料,分析不同载体应用的优缺点,重点综述了载体的改性手段。研究表明,载体经过改性可调节载体表面酸碱性、化学官能团的分布从而增强载体与活性组分的相互作用、提高活性组分分散度、稳固活性组分价态,最终提高催化剂活性和稳定性;其中氮改性的炭材料被认为是乙炔氢氯化最有工业化应用前景的载体。     

雷公藤红素与人血清白蛋白的相互作用

通过使用荧光光谱、分光光度法以及等温滴定量热法等方法,研究了人血清白蛋白(HSA)与雷公藤红素的结合方式,采用分子对接的方式分析相互作用模式。荧光光谱结果可知,雷公藤红素与HSA主要通过氢键和范德华力结合,并且雷公藤红素猝灭HSA内源荧光的机制为静态猝灭,同时两者的结合过程主要受温度影响。在两者的结合过程中,会导致HSA的构象与微环境发生微小的改变。结合分子对接结果可知,两者的结合过程可能主要是通过疏水相互作用、范德华力等弱相互作用进行结合。为雷公藤红素在血液中的运输及传递提供了理论支持,对深入理解雷公藤红素的药效学和药代动力学性质具有重要的意义。     

双氟磺草胺与牛血清白蛋白相互作用的研究

1 引言 蛋白质是生命现象的物质基础。而血清白蛋白作为载体蛋白，对脂肪酸、氨基酸、金属离子及药物等在血浆中的传输、分配及新陈代谢等起着重要作用，因此研究各种试剂与血清蛋白之间的相互作用已成为化学、生命科学和临床医学等领域的热点。HSA是由585个氨基酸残基组成的单肽链蛋白质，分子量约为66500。     

龙胆药理作用的研究进展

龙胆是中国中药传统药材之一。现代中药研究发现龙胆中可分离出多种具有药理活性的化学组分,且除传统理念上的保肝护肝作用外,龙胆的一些其他药理作用也随之浮出水面。近年来龙胆在中药研究领域及临床应用上可谓是炙手可热,本文对龙胆药理作用进行总结,为龙胆的进一步研究与应用提供参考。     

大气压等离子体射流气源组分研究进展

大气压等离子体射流(APPJ)作为一个新型的大气压冷等离子体放电技术,其在大气压下产生,射流温度接近室温,化学活性高,在生物医学、材料化学和环境卫生等研究领域的应用成为研究热点。随着对大气压等离子体射流应用研究的不断深入,发现APPJ气源组分对其应用研究产生了很大的影响。APPJ气源组分会影响其放电特性、发射光谱和化学特性,其中APPJ中各种化学活性粒子在其应用研究中起到重要作用,APPJ气源成分主要影响化学活性粒子的种类与浓度,这些因素会影响APPJ技术成本和处理效率。因此,本文综述了在不同气源组分条件下大气压等离子体射流的放电特性、发射光谱和化学特性以及在微生物灭活、表面改性和表面清洁中的应用研究,分析总结了气源组分对APPJ应用方面的影响作用并展望了其研究前景。     

Co—Mo系统硫变换催化剂的红外光谱表征研究

采用双探针（CO，CO＋NO）原位红外光谱方法对单组分Co，Mo及双组分Co-Mo系耐硫变换进行研究，结果表明：在载体AI2O3上，活性组Co，Mo与载体之间的相互作用较强，而在载体AI2O3－MgO上，活性组分Co、Mo与载体之间的相互作用适中，且活性组分Co、Mo之间存在协调作用，提高了催化剂的变换活性。     

不同相对分子质量的海藻酸钠与人血清白蛋白相互作用的研究

通过加酸微波降解海藻酸钠联合凝胶色谱柱分离的方式制备了相对分子质量为3190、4897、6800、14635、20960、66500的6种不同相对分子质量的海藻酸钠。采用荧光猝灭法研究了6种不同相对分子质量的海藻酸钠与HSA的相互作用。实验结果表明,海藻酸钠与HSA存在相互作用,两者结合属于静态猝灭;热力学分析表明6种不同相对分子质量的海藻酸钠和HSA的相互作用是以氢键和范德华力为主的分子间作用。相对分子质量的变化并没影响其猝灭类型及作用力类型。结合位点数约为1。两者结合常数受相对分子质量的影响较大,在海藻酸钠相对分子质量为3190~66500之间其结合常数呈现为先增加后减小的趋势。     

植物病害化学防治的新思路

在病原物-寄主的互作关系中,利用和发挥化学药剂抑制病原物的生长、繁殖和侵染以及诱导寄主抗病性的协同作用,控制病害的发生流行,可以为植物病害化学防治的新途径。     

Chemotherapeutic engineering: Application and further development of chemical engineering principles for chemotherapy of cancer and other diseases

This review defines chemotherapeutic engineering as an engineering discipline that applies and further develops chemical engineering principles, techniques and devices for chemotherapy of cancer and other diseases. It provides new challenges as well as new opportunities for chemical engineering. Chemical engineering has substantially changed the human civilization through its services and products to improve the quality of life for human being. It is now time for chemical engineering to contribute to the most important aspect of the quality of life—human health care. Cancer and cardiovascular diseases are the leading causes for deaths. Chemotherapy is one of the most important treatments currently available for cancer and other diseases such as cardiovascular diseases. The present status of chemotherapy is far from being satisfactory. Its efficacy is limited and patients have to suffer from serious side effects, some of which are life-threatening. Chemotherapeutic engineering is emerging to help solving the problems in chemotherapy and to eventually develop an ideal way to conduct chemotherapy with the best efficacy and the least side effects. This review gives, from an engineering point of view, brief introductions to cancer and cancer treatment, chemotherapy and the problems involved in chemotherapy, and the possible roles of chemical engineering in solving the problems involved. Progress in developing various controlled and targeted drug delivery systems is reviewed with an emphasis on nanoparticles of biodegradable polymers and lipid bilayer vesicles (liposomes). Preparation, characterization, in vitro release, cell line experiments and animal testing of drug-loaded polymeric nanoparticles are described with paclitaxel as a prototype drug, which is one of the best anticancer drugs found in nature. A novel drug delivery system, liposomes-in-microspheres, is used as an example for possible combinations of the existing polymer- and lipid-based delivery systems. Research of molecular interactions between the drug and the cell membrane is also reviewed, with the lipid monolayer at the air-water or oil-water interface and bilayer vesicles as models for the cell membrane. Finally, mathematical modeling in chemotherapeutic engineering is discussed with typical examples in the literature. This review is a short introduction of chemotherapeutic engineering to chemical engineers, biomedical engineers, other engineers, clinical oncologists, and pharmaceutical scientists, who are interested in developing new dosage forms of drugs for chemotherapy of cancer and other diseases with the best efficacy and the least side effects.     

Fungal aerosols: A review

Fungal aerosols are important in the spread of plant, animal and human diseases. The development of this area of aerobiology is reviewed in relation to its influence on, and interaction with, the growth of aerosol science. Physical characteristics of airborne fungal spores relevant to their liberation, flight and deposition are discussed. Some samplers and sampling techniques especially suited to fungal aerosols are described.     

Chemical Biology Toolbox to Visualize Protein Aggregation in Live Cells

Protein misfolding and aggregation is a complex biochemical process and has been associated with numerous human degenerative diseases. Developing novel chemical and biological tools and approaches to visualize aggregated proteins in live cells is in high demand for mechanistic studies, diagnostics, and therapeutics. In this review, we summarize the recent developments in the chemical biology toolbox applied to protein aggregation studies in live cells. These methods exploited fluorescent protein tags, fluorescent chemical tags, and small-molecule probes to visualize the protein-aggregation process, detect proteome stresses, and quantify the protein homeostasis network capacity. Inspired by these seminal works, we have generalized design principles for the development of new detection methods and probes in the future that will illuminate this important biological process.     

The Role of Trp79 in β-Actin on Histidine Methyltransferase SETD3 Catalysis

N^τ-methylation of His73 in actin by histidine methyltransferase SETD3 plays an important role in stabilising actin filaments in eukaryotes. Mutations in actin and overexpression of SETD3 have been related to human diseases, including cancer. Here, we investigated the importance of Trp79 in β-actin on productive human SETD3 catalysis. Substitution of Trp79 in β-actin peptides by its chemically diverse analogues reveals that the hydrophobic Trp79 binding pocket modulates the catalytic activity of SETD3, and that retaining a bulky and hydrophobic amino acid at position 79 is important for efficient His73 methylation by SETD3. Molecular dynamics simulations show that the Trp79 binding pocket of SETD3 is ideally shaped to accommodate large and hydrophobic Trp79, contributing to the favourable release of water molecules upon binding. Our results demonstrate that the distant Trp79 binding site plays an important role in efficient SETD3 catalysis, contributing to the identification of new SETD3 substrates and the development of chemical probes targeting the biomedically important SETD3.     

Unveiling the Hidden Theatre of Microbes

The chemical interactions of microbes shape and structure their communities and have important effects on the health and diseases of multicellular hosts. This special collection on Microbial Biosynthesis and Interactions sheds light on some of these interactions and takes a closer look at the molecules involved in them.     

From Channels to Canonical Wnt Signaling: A Pathological Perspective

Wnt signaling is an important pathway mainly active during embryonic development and controlling cell proliferation. This regulatory pathway is aberrantly activated in several human diseases. Ion channels are known modulators of several important cellular functions ranging from the tuning of the membrane potential to modulation of intracellular pathways, in particular the influence of ion channels in Wnt signaling regulation has been widely investigated. This review will discuss the known links between ion channels and canonical Wnt signaling, focusing on their possible roles in human metabolic diseases, neurological disorders, and cancer.     

Screening of Inhibitors Targeting Heat Shock Protein 47 Involved in the Development of Idiopathic Pulmonary Fibrosis

Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is causally related to fibrotic diseases, including idiopathic pulmonary fibrosis. The identification of Compounds that interfere with the HSP47-collagen interaction is essential for the development of relevant therapeutics. Herein, we prepared human HSP47 as a soluble fusion protein expressed in E. coli and established an assay system for HSP47 inhibitor screening. We screened a natural and synthetic Compound library established at Nagasaki University. Among 1023 Compounds, 13 exhibited inhibitory activity against human HSP47, of which three inhibited its function in a dose-dependent manner. Epigallocatechin-3-O-gallate, one of these three Compounds, is a typical polyphenol Compound derived from tea leaves. Structurally related Compounds were synthesized and examined for their activity, revealing a hydroxyl group at A-ring position 5 as important for its activity. The present findings provide valuable insight for the development of natural product-derived therapeutics for fibrotic diseases, including idiopathic pulmonary fibrosis.     

Discovery of Small-Molecule Modulators of Protein–RNA Interactions by Fluorescence Intensity-Based Binding Assay

Protein–RNA interactions mediate various cellular processes, the dysregulation of which has been associated with a list of diseases. Thus, novel experimental tools for monitoring protein–RNA interactions are highly desirable to identify new chemical modulators of these therapeutic targets. In this study, we constructed simple fluorescence intensity-based protein–RNA binding assays by testing multiple environment-sensitive organic fluorophores. We selected the oncogenic interaction between Lin28 and the let-7 microRNA and the important immunomodulatory Roquin–Tnf CDE interaction as representative targets. We adapted this assay to high-throughput screening for the identification of pyrazolyl thiazolidinedione-type molecules as potent small-molecule inhibitors of protein–microRNA interactions. We clearly showed the structure–activity relationships of this new class of Lin28–let-7 interaction inhibitors, and confirmed that cellular mature let-7 microRNAs and their target genes could be modulated upon treatment with the pyrazolyl thiazolidinedione-type inhibitor. We expect that our simple and adaptable screening approach can be applied for the development of various assay systems aimed at the identification of bioactive small molecules targeting protein–RNA interactions.     

Novel Strategies for Drug Discovery Based on Intrinsically Disordered Proteins (IDPs)

Intrinsically disordered proteins (IDPs) are proteins that usually do not adopt well-defined native structures when isolated in solution under physiological conditions. Numerous IDPs have close relationships with human diseases such as tumor, Parkinson disease, Alzheimer disease, diabetes, and so on. These disease-associated IDPs commonly play principal roles in the disease-associated protein-protein interaction networks. Most of them in the disease datasets have more interactants and hence the size of the disease-associated IDPs interaction network is simultaneously increased. For example, the tumor suppressor protein p53 is an intrinsically disordered protein and also a hub protein in the p53 interaction network; α-synuclein, an intrinsically disordered protein involved in Parkinson diseases, is also a hub of the protein network. The disease-associated IDPs may provide potential targets for drugs modulating protein-protein interaction networks. Therefore, novel strategies for drug discovery based on IDPs are in the ascendant. It is dependent on the features of IDPs to develop the novel strategies. It is found out that IDPs have unique structural features such as high flexibility and random coil-like conformations which enable them to participate in both the "one to many" and "many to one" interaction. Accordingly, in order to promote novel strategies for drug discovery, it is essential that more and more features of IDPs are revealed by experimental and computing methods.