A review of advances and new developments in the analysis of biological volatile organic compounds

Biological volatile organic compounds (VOCs) are interlinked to biological metabolism and bacterial populations localized on the surfaces of biological samples. The characteristics of biological VOCs at different physiological status or metabolism phases are various, which contain crucial bio-information. In this review, the significance of the study of biological VOCs was introduced, and crucial techniques greatly influencing the investigation were summarized and reviewed including efficient sampling, suitable analytical and bio-information distillation techniques. From the preliminary identification of biological VOC components to the interpretation of biological VOC characteristics is a great improvement in this field, which would provide more abundant bio-information during biological metabolism. Owing to complicated biological VOC compositions, any single sampling or bio-information distillation method could not obtain complete biological VOCs and interpret the biological VOC characteristics, and would result in the loss of effective bio-information. The combination of some suitable sampling and bio-information distillation techniques for the study of biological VOCs and the related bio-information will be a novel trend in the future.     

A novel electrochemical microsensor for the determination of NO and its application to the study of the NO donor S-nitrosoglutathione

A novel electrochemical microsensor for the determination of NO based on an electropolymerized film of tetraaminophthalocyaninecopper [Cu(TAPc)] was prepared. Its response to NO and its application to the study of an NO donor (S-nitrosoglutathione; GSNO) are also described. The microsensor exhibited an electrocatalytic effect on NO oxidation and showed a low detection limit, high sensitivity and selectivity for NO determination. The oxidation current (measured by differential pulse amperometry) was linear for NO concentrations ranging from 6.2 x 10(-9) to 3.0 x 10(-5) mol L-1 with a calculated detection limit of 4.0 x 10(-9) mol L-1 (S/N = 3) and a linear coefficient of 0.9984. Some endogenous electroactive substances in biological tissues, such as dopamine, 5-hydroxytryptamine and nitrite, at concentrations higher than those in biological systems did not interfere with NO determination. The sensor shows promise for the possible in vivo determination of NO. Using the microsensor, the NO release from the NO donor (GSNO) was successfully monitored. This work sets a foundation for the study of the pharmacology and the biological effects in vivo of S-nitrosothiols.     

Application of restricted access material (RAM) with precolumn-switching and matrix solid-phase dispersion (MSPD) to the study of the metabolism and pharmacokinetics of Verapamil

In the pharmaceutical industry, studies of the metabolism and pharmacokinetics of drugs are important routine applications which require the analysis of the precursor drug and its metabolites in various biological matrices, such as plasma, serum, urine, cell culture media and tissue samples. In this study, two new and simple methods of sample preparation were optimized and validated: on the one hand, a column-switching technique with a restricted access material (RAM) was used to analyze biological fluids, and on the other hand, matrix solid-phase dispersion (MSPD) was applied to the extraction of analytes from tissue samples. Identification of the metabolites was done with a LC-MS system (ion trap in the MS(n)mode) coupled both on-line (RAM) and off-line (MSPD).Using the common calcium antagonist Verapamil, it is shown that these two methods allow rapid identification of phase I and phase II metabolites from biological samples and are suitable for pharmacokinetic and pharmacodynamic studies of pharmaceuticals in biological matrices.     

Plasmonic Resonant Nanoantennas Induce Changes in the Shape and the Intensity of Infrared Spectra of Phospholipids

Surface enhanced infrared absorption spectroscopic studies (SEIRAS) as a technique to study biological molecules in extremely low concentrations is greatly evolving. In order to use the technique for identification of the structure and interactions of such biological molecules, it is necessary to identify the effects of the plasmonic electric-field enhancement on the spectral signature. In this study the spectral properties of 1,2-Dipalmitoyl-sn-glycero-3 phosphothioethanol (DPPTE) phospholipid immobilized on gold nanoantennas, specifically designed to enhance the vibrational fingerprints of lipid molecules were studied. An AFM study demonstrates an organization of the DPPTE phospholipid in bilayers on the nanoantenna structure. The spectral data were compared to SEIRAS active gold surfaces based on nanoparticles, plain gold and plain substrate (Si) for different temperatures. The shape of the infrared signals, the peak positions and their relative intensities were found to be sensitive to the type of surface and the presence of an enhancement. The strongest shifts in position and intensity were seen for the nanoantennas, and a smaller effect was seen for the DPPTE immobilized on gold nanoparticles. This information is crucial for interpretation of data obtained for biological molecules measured on such structures, for future application in nanodevices for biologically or medically relevant samples.     

Comparative study of the biological activity of organosilicon and organogermanium compounds

The literature data and the results of our own investigations on the comparative study of the biological activity of isostructural organogermanium and organosilicon compounds have been summarized. It has been shown that the series of organogermanium and organosilicon compounds is more active than the carbon analogues, the majority of organogermanium compounds are less toxic than the sila analogues, the biological activity of the compounds under study appears to be similar but can dramatically differ in the degree of activity, and, moreover, in some particular cases sila and germa analogues exhibit the opposite biological effects.     

Computational modeling of the human serum proteome response to colon resection surgery

Principal component analysis (PCA) is much used in exploring time-course biological data sets, but does not distinguish variation between time and subjects. This study proposes a new integrated approach by combining analysis of variance (ANOVA) and three component modeling methods. The former was used to separate the between- and within-subject variation, and the latter represent modeling strategies on a scale moving from commonality to individuality. The proposed approach was applied to a surface-enhanced laser desorption and ionization time of flight mass spectrometry (SELDI-TOF-MS) data set of a serum protein expression time course before and after colon resection. Two common biological processes are identified and individual differences among patients were also detected, and the biological relevance of both is discussed.     

Synthesis of Pyrimidine and Pyran Derivatives with the Related Systems and the Study of Their Behavior in the Liquid Solutions

This study aims to synthesis of condensed and non‐condensed heterocyclic rings with long fatty chains as surface active biological compounds. 2‐Cyano‐3‐(dimethylamino)‐N‐octadecylacrylamide ( 5 ) was used to synthesize pyrimidine, pyran, and other condensed products by interacting with appropriate chemical reagents. These compounds were transferred to nonionic surface‐active agents by condensation with propylene oxide. The surface and biological properties showed that these compounds have a high solubility that helps them in easy absorption and adsorption with other compounds. In addition, they have a high ability to decrease the surface tension of the liquids, good wetting, and emulsification power, which can be used at different temperatures without losing their surface or biological properties and enable them for use in industrial and pharmaceutical purposes easily.     

On the possibility of the nitric oxide formation upon biotransformation of hydroxamic acids

Taking into account the data on oxidative transformation of hydroxamic acids to form nitric oxide and the similarity of their structure to the hydroxyarginine group being involved in the NO synthesis, we performed the study of biotransformation of salicylhydroxamic acid and N(4)-hydroxyasparagine in the liver tissues. According to the data from ESR spectroscopy, the compounds under study are inefficient NO donors in a biological system and their biological activities are mainly defined by the ability to chelate metal ions.     

Prediction of biological activity spectra via the Internet

The majority of biologically active compounds have both pharmacotherapeutic and side/toxic actions. To estimate general efficacy and safety of the molecules under study, their biological potential should be thoroughly evaluated. In an early stage of study, only information about structural formulae was available and was used as an input for computational prediction. Based on a structural formulae of compounds presented as SDF or MOL-files, computer program PASS predicts 900 pharmacological effects, mechanism of action, and specific toxicity. An average accuracy of prediction in leave-one-out cross-validation is about 85%. For evaluating new compounds, scientific community may use PASS via the Internet for free at URL: http://www.ibmh.msk.su/PASS. In the first 18 months of PASS Inet's use, approximately 1000 researchers from 60 countries have obtained predicted biological activity spectra for about 23,000 different chemical compounds. More than 64 million PASS predictions for almost 250,000 compounds from Open NCI database are available on the web site http://cactus.nci.nih.gov/ncidb2/. These predictions are used for selecting compounds with desirable and without unwanted types of biological activities among the NCI samples available for screening.     

适配体功能化多壁碳纳米管整体柱分离富集细胞色素c

本文结合核酸适配体的特异性吸附及碳纳米管比表面积大的特点,研制了核酸适配体功能化碳纳米管/聚合物复合整体柱(AMMC),并将其应用于细胞色素c(Cyt c)选择性分离。结果表明,AMMC具有良好的通透性和稳定性,可选择性富集Cyt c,富集量可达1.47 mg。结合顺序注射系统,AMMC成功用于猪心样品中Cyt c的选择性分离富集,在生物样品分析中具有良好的应用前景。     

Toward understanding the mechanism of chromophore-assisted laser inactivation--evidence for the primary photochemical steps

Chromophore-assisted laser inactivation (CALI) is a light-mediated technique used to selectively inactivate proteins of interest to elucidate their biological function. CALI has potential applications to a wide array of biological questions, and its efficiency allows for high-throughput application. A solid understanding of its underlying photochemical mechanism is still missing. In this study, we address the CALI mechanism using a simplified model system consisting of the enzyme beta-galactosidase as target protein and the common dye fluorescein. We demonstrate that protein photoinactivation is independent from dye photobleaching and provide evidence that the first singlet state of the chromophore is the relevant transient state for the initiation of CALI. Furthermore, the inactivation process was shown to be dependent on oxygen and likely to be based on photooxidation of the target protein via singlet oxygen. The simple model system used in this study may be further applied to identify and optimize other CALI chromophores.     

Synthesis and biological evaluation of the geometric farnesylated analogues of the a-factor mating peptide of Saccharomyces cerevisiae

The a-factor of Saccharomyces cerevisiae is a dodecapeptide pheromone (YIIKGVFWDPAC(Farnesyl)-OCH(3), 1), in which post-translational modification with a farnesyl isoprenoid and carboxymethyl group is required for full biological activity. This peptide has been used as a model system to explore the biological function of the farnesylcysteine moiety, which is found on and required for the biological activity of many key mammalian proteins. The objective of this particular study was the determination of the biological effect of double bond isomerization of the natural E, E-farnesyl moiety on the biological activity of the a-factor. A unified, stereoselective synthetic route to the three geometric isomers of E,E-farnesol (12, 13, and 14) has been developed. The key feature of this synthesis is the ability to control the stereochemistry of triflation of the beta-ketoester 22 to give either 23 or 25. The three farnesol isomers were converted to the corresponding isomeric a-factors (9, 10 and 11) via a modified version of a previously utilized synthetic route. Biological evaluation of these peptides indicates that, surprisingly, all three possess nearly equivalent activity to the natural a-factor bearing the E,E-farnesyl moiety.     

Study on the Electrochemical Behavior of Melatonin with Modified Electrode

Melatonin, N-acetyl-5-methoxytryptamine, is an indoleamine hormone synthesized in the pinealocytes. It has been considered as a time-keeping hormone at the biological clocks and was found to play central role in cell protection^[1]. Melatonin in biological samples can be detected by several methods, such as HPLC, UV, fluorimetry and radio-immunoassay. However, only a few studies dealing with its redox behavior have been reported^[1-3]. The aim of the present study is to use the activating electrochemical modified glassy carbon electrode(MGCE) for the preconcentration and trace determination of melatonin.     

Biological fingerprinting analysis of the interactome of a kinase inhibitor in human plasma by a chemiproteomic approach

In this study, a gel free chemiproteomic method based on chromatography was developed and applied for the biological fingerprinting analysis of complex biological system. p-Aminobenzamidine (ABA), an inhibitor of trypsin-like serine proteases, was immobilized for characterizing their interacting proteins in human plasma. By the proteomic analysis method, 214 proteins were identified with obvious affinity to the immobilized ABA. By searching the sequences of above proteins with consensus patterns of the two active sites, seven proteins belong to trypsin-like serine protease group were found. Based on the Gene Ontology annotation, the identified trypsin-like serine proteases have the function of catalytic activity and calcium ion binding, and are mainly involved in the biological process of blood coagulation. Eight more other proteins related to calcium ion binding and blood coagulation were found. Nearly all of these proteins cannot be identified by directly analyzing the plasma sample demonstrating the chemiproteomics a useful approach to characterize interacting proteins in the low abundance range.     

Electrochemical study of dopamine and noradrenaline at the water/1,6-dichlorohexane interface

Interfaces between two immiscible electrolyte solutions are recognized as a simplified model for biological systems and they can be of great relevance to the characterization of biomolecules and their role in biological systems. In this work, ion transfer and facilitated ion transfer of protonated catecholamines (dopamine and noradrenaline) by dibenzo-18-crown-6 are investigated at the water/1,6-dichlorohexane interface. The formation constant of the complex between both dopamine and noradrenaline with dibenzo-18-crown-6 was evaluated and the experimental conditions for the analytical determination of those catecholamines are established. These results can improve the understanding of the pharmacodynamics of the catecholamines, and contribute to the study of their interaction with biological membranes. Furthermore it can be used to develop an alternative method for the determination of neural signal transmission catecholamines.     

Comparison of the Effects of Biofouling on Voltammetric and Potentiometric Measurements

Biofouling of sensors is a common problem when measuring biological samples. The adherence of proteins and biomolecules, called hemostasis, is the first of four steps that lead to biofouling and eventually a foreign body response. This typically occurs within the first hours after the exposure of the biosensor to a biological sample. The purpose of this study was to assess the effect of this initial step of biofouling on cyclic voltammetry and potentiometric measurements. The results show that biofouling occurred rapidly within minutes and strongly affected cyclic voltammetry measurements, while potentiometric measurements were minimally affected even after 24 hours.     

Experimental and Theoretical Study of the Stability of the Complex Fisetin–Cu(II) and A Comparative Study of Free Ligand and Complex Interaction with Molecular Singlet Oxygen

In this work, the flavonol fisetin was selected in order to study its reactivity against Cu(II), a metal ion of interest in biological media and industry. The stoichiometry and apparent formation constant of the complex in ethanolic medium at 25°C were evaluated using spectrophotometric techniques. The resulting stoichiometry was a 1:1 ligand:metal complex, and a log K = 5.17 ± 0.12 was determined. Since two possible chelation sites can be proposed for the complex formation, quantum chemistry calculations were performed on these structures. Calculations suggest that the hydroxyl-keto site is more stable for the complex formation than the catechol site. Flavonoids could exert protection against oxidative damage caused by reactive oxygen species, and this biological activity could be affected by chelation with metal ions. This led us to perform a study on the interaction of both, free flavonoid and complex, with reactive oxygen species. Our results showed both compounds quench molecular singlet oxygen photogenerated with visible light, mainly in a physical fashion. In order to analyze a possible protective effect of flavonoid and its complex against oxidative damage in biological environments, the amino acid tryptophan was selected as a model oxidation system. Free flavonoid does not have a marked protective effect, whereas its complex showed a relevant protective effect.     

皂甙研究: 糖链的作用

本文收集了近年来一些有关皂甙的分子结构和生物活性的研究结果，较系统地总结了皂甙中糖链的结构对其生物活性的影响，并提出了糖链在这类物质中的生物学意义的问题。     

Rosin Derivatives as a Platform for the Antiviral Drug Design

The increased complexity due to the emergence and rapid spread of new viral infections prompts researchers to search for potential antiviral and protective agents for mucous membranes among various natural objects, for example, plant raw materials, their individual components, as well as the products of their chemical modification. Due to their structure, resin acids are valuable raw materials of natural origin to synthesize various bioactive substances. Therefore, the purpose of this study was to confirm the possibility of using resin acid derivatives for the drug design. As a result, we studied the cytotoxicity and biological activity of resin acid derivatives. It was shown that a slight decrease in the viral load in the supernatants was observed upon stimulation of cells (II) compared with the control. When using PASS-online modeling (Prediction of Activity Spectra for Substances), the prediction of the biological activity spectrum showed that compound (I) is capable of exhibiting antiviral activity against the influenza virus. The use of the SWISS-ADME webserver to reveal the drug-like properties of compounds did not directly indicate the presence of antiviral activity. These results indicate the potential of resin acid derivatives as a starting point for extensive research in the study of biological activity.