Investigation of substituent effect of 1-(3,3-diphenylpropyl)-piperidinyl phenylacetamides on CCR5 binding affinity using QSAR and virtual screening techniques

Summary A linear quantitative–structure activity relationship model is developed in this work using Multiple Linear Regression Analysis as applied to a series of 51 1-(3,3-diphenylpropyl)-piperidinyl phenylacetamides derivatives with CCR5 binding affinity. For the selection of the best variables the Elimination Selection-Stepwise Regression Method (ES-SWR) is utilized. The predictive ability of the model is evaluated against a set of 13 compounds. Based on the produced QSAR model and an analysis on the domain of its applicability, the effects of various structural modifications on biological activity are investigated. The study leads to a number of guanidine derivatives with significantly improved predicted activities.     

Novel affinity chromatography method for the efficient purification of recombinant Binder of SPerm homolog proteins

In mammalian species, a family of proteins named the Binder of SPerm proteins, which are expressed in the male reproductive tract, have been shown to play a role in epididymal sperm maturation and sperm capacitation. Recently, one homolog from human and two homologs from mouse were characterized. In order to further investigate the biochemical activity of these proteins, efficient purification procedures are required to isolate the proteins. Since these proteins are produced in very minute quantities, we exploited the high capacity of Escherichia coli to produce larger quantities of recombinant proteins that were subsequently purified using affinity chromatography on a diethylaminoethyl‐Sephadex A‐25 column. Binder of SPerm proteins have been shown to interact with pseudo‐choline groups such as diethylaminoethyl through affinity rather than ionic interactions. The aim of the current study was to develop a novel method for purifying these recombinant proteins, produced in Escherichia coli cells. Diethylaminoethyl is positively charged and is a weak anion exchanger, but binder of sperm proteins interacts with affinity to this resin. This study presents a new, rapid, and cost‐effective purification method that provides with an exceptional purity level, which can be used to study their roles in mammalian fertilization.     

The Application of Fluorine‐Containing Reagents in Structural Proteomics

Structural proteomics refers to large‐scale mapping of protein structures in order to understand the relationship between protein sequence, structure, and function. Chemical labeling, in combination with mass‐spectrometry (MS) analysis, have emerged as powerful tools to enable a broad range of biological applications in structural proteomics. The key to success is a biocompatible reagent that modifies a protein without affecting its high‐order structure. Fluorine, well‐known to exert profound effects on the physical and chemical properties of reagents, should have an impact on structural proteomics. In this Minireview, we describe several fluorine‐containing reagents that can be applied in structural proteomics. We organize their applications around four MS‐based techniques: a) affinity labeling, b) activity‐based protein profiling (ABPP), c) protein footprinting, and d) protein cross‐linking. Our aim is to provide an overview of the research, development, and application of fluorine‐containing reagents in protein structural studies.     

Screening of cardioprotective diseases bioactive components from Danshen extracts and LC–MS analysis

A rapid and efficient analysis and screening method is adopted for cell affinity capture coupled with HPLC–MS (CAC–HPLC–MS) analysis of bioactive components that have possible efficiency against cardiovascular diseases. This method involves affinity capture, concentration, and separation of bioactive components from Danshen library using oxidatively damaged endothelial cells induced by H₂O₂, as well as analysis and identification of targeted compounds with HPLC and MS. It combines the specific interaction between cell membrane receptors and bioactive components with the powerful analysis and identification function of HPLC–MS. The CAC–HPLC–MS method was also used for analysis and screening of bioactive components from crude extracts of Danshen. A total of 19 components were found to be bound to oxidatively damaged endothelial cells with seven of these identified. Existing literature confirms that these seven components have many activities related to cardioprotective diseases. Therefore, the combination of biological affinity capture with HPLC–MS should be regarded as an attractive method with great potential for rapid and efficient screening of bioactive components related to anti-cardiovascular diseases from natural product libraries.     

Syntheses,crystal structure and biological evaluation of three novel Cu (II) complexes with Schiff base derived from fluorinated amino acid and Salicylaldehyde

Three novel Cu (II) coordination complexes, formulated as [Cu₃(C₁₄H₈NO₃F) ₂ (CH₃COO)₂]_n ( 1 ), [Cu₂(C₁₄H₉NO₃F)₂(CH₃COO)Cl] ( 2 ) and [Cu(C₁₄H₈NO₃F)(CH₃OH)₂] ( 3 ), have been synthesized by 3-Fluoroanthranilic acid, Salicylaldehyde and Cu (II) salt as sources in different reaction conditions and characterized by single crystal X-ray diffraction, X-ray powder diffraction, IR spectroscopy and elemental analysis. Single-crystal diffraction analysis revealed that the complexes exhibited different coordination modes and conformations which were linked into multidimensional networks through some weak interactions. The biological activities vary greatly on account of the different Cu (II) numbers among the three complexes. In order to discuss the bioactivities, the complexes have been screened for antimicrobial activities against E. coli and S. aureus, antitumor activities against A549 (human lung cancer cells), Hela (human cervical cancer cells) and HepG-2(human liver hepatocellular carcinoma cells). Their interactions with calf thymus DNA were investigated by UV–visible and fluorescence spectrometry, as well as viscosity measurements. Interestingly, 1 (the rare 3-core Cu (II) coordination polymer) shows great antibacterial activities and highest DNA binding affinities. Antitumor studies revealed that complex 1 also exhibited highest activity.     

A theoretical investigation of the electronic and geometrical structure of silicon fluorides SiF n and their anions SiF n −,n=1−6

The electronic and geometrical structure of the ground and low-lying excited states of the SiF _n and SiF_n ^– series (n = 1-6) are calculated using the density functional method. Energies of fragmentation through different decay channels were evaluated for both series and found to be in good accord with the experimental data and results of nonempirical calculations. The adiabatic electron affinity (EA) of the neutral series is estimated for the first time. The SiF₄ ^– anion is shown to be stable toward dissociation though its neutral precursor possesses adiabatic EA close to zero. The SiF₅ ^– and SiF₆ ^– anions are stable toward dissociation in the gas phase; however, the neutral radical SiF₅ is near the stability threshold and SiF₆ is unstable as regards dissociation to SiF₄+F₂. An interesting peculiarity of the silicon fluoride anions is their similar energy of F-detachment, i.e. the affinities of all the neutral SiF_n, (n = 0-5) for the fluoride anion are similar.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 44–53, January, 1993.     

水油两相体系生物还原-化学沉淀耦合反应制备纳米二硫化锡

针对Sn4+易于水解而难以在水相稳定存在的不利条件,尝试了在水油两相体系中应用生物转化-化学沉淀耦合反应工艺制备SnS2纳米材料。研究了水油两相体系制备SnS2的优化条件,并借助XRD、SEM、EDS表征了制备材料的结构、形貌和物相。研究表明,生物水相pH值7、水油两相反应温度35℃,油相Sn4+与水相SO42-之物质的量浓度比1∶2的条件下有利于SnS2的生成。制备的SnS2为纳米片花瓣,纳米片平均厚度约为30 nm,花状微晶直径约1~5μm,纯度高,无杂质。     

Calculation of the proton affinities of polychlorobenzenes and the activation energies of 1,2-hydrogen shifts in arenonium ions

The proton affinities of benzene, chlorobenzene and polychlorobenzenes with the common formula C₆Cl _n H_6–n (n=0–6) have been calculated by the AM1 method. The proton affinity averaged over the protonated isomers increases monotonically asn growing from 0 to 5, and then decreases when passing from pentato hexachlorobenzene. The energies of proton addition to the different positions in the polychlorobenzene molecules have been estimated. It has been found that unsubstituted carbon atoms are preferred for proton attack. The positions with the highest proton affinity are the carbon atoms with the largest negative charges. The activation energies of 1,2-hydrogen shifts in arenonium ions of the polychlorobenzenes have been calculated.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1213–1217, July, 1993.     

Affinity adsorption mechanism studies of adsorbents C1-Zn(Ⅱ) for uremic middle molecular peptides containing Asp-Phe-Leu-Ala-Glu sequence

To exploit efficient adsorbents for removing middle molecular peptides containing DFLAE (DE5,a typical peptide sequence accumulated in uremic serum) sequence by hemoperfusion,we designed and synthesized three affinity adsorbents (C1-Zn2+,C2-Zn2+ and C3-Zn2+) that could have high affinity to DE5.Subsequently,we evaluated the corresponding adsorption ability of each adsorbent by static adsorption experiments and isothermal titration calorimetry (ITC).The results showed that C1-Zn2+ had the best adsorption abi...