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101.
Grieco P Carotenuto A Patacchini R Maggi CA Novellino E Rovero P 《Bioorganic & medicinal chemistry》2002,10(12):3731-3739
Human urotensin II (hU-II; H-Glu-Thr-Pro-Asp-cyclo[Cys-Phe-Trp-Lys-Tyr-Cys]-Val-OH) is a disulfide bridged undecapeptide recently identified as the ligand of an orphan G protein-coupled receptor. hU-II has been described as the most potent vasoconstrictor compound identified to date. With the aim of replacing the disulfide bridge by a chemically more stable moiety, we have synthesized and tested a series of lactam analogues of hU-II minimum active fragment, that is hU-II(4-11). The contractile activity of the synthetic analogues on the rat isolated thoracic aorta was found to be dependent upon the dimension of the lactam bridge. The most active peptide, H-Asp-cyclo[Orn-Phe-Trp-Lys-Tyr-Asp]-Val-OH (3), is approximately 2 logs less potent than hU-II (pD(2)=6.3 vs 8.4). A conformational analysis in solution of the active peptide 3, one of the inactive analogues, and hU-II was performed, using NMR and molecular modelling techniques. A superposition of the calculated structures of hU-II and 3 clearly shows that three out of four key residues (i.e., Phe(6), Lys(8) and Tyr(9)) maintain the same side- chain orientation, while the fourth one, Trp(7), cannot be superimposed. This observation could explain the reduced biological activity of the synthetic analogue. 相似文献
102.
Vincent Zecchini Basetti Madhu Roslin Russell Nelma Pértega‐Gomes Anne Warren Edoardo Gaude Joana Borlido Rory Stark Heather Ireland‐Zecchini Roheet Rao Helen Scott Joan Boren Charlie Massie Mohammad Asim Kevin Brindle John Griffiths Christian Frezza Ian G Mills 《The EMBO journal》2014,33(12):1365-1382
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Angela Avenoso Gabriella Facciol Monica Salemi Edoardo Spina 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2000,746(2):159
A simple and sensitive high-performance liquid chromatographic (HPLC) method with UV absorbance detection is described for the quantitation of risperidone and its major metabolite 9-hydroxyrisperidone in human plasma, using clozapine as internal standard. After sample alkalinization with 1 ml of NaOH (2 M) the test compounds were extracted from plasma using diisopropyl ether–isoamylalcohol (99:1, v/v). The organic phase was back-extracted with 150 μl potassium phosphate (0.1 M, pH 2.2) and 60 μl of the acid solution was injected into a C18 BDS Hypersil analytical column (3 μm, 100×4.6 mm I.D.). The mobile phase consisted of phosphate buffer (0.05 M, pH 3.7 with 25% H3PO4)–acetonitrile (70:30, v/v), and was delivered at a flow-rate of 1.0 ml/min. The peaks were detected using a UV detector set at 278 nm and the total time for a chromatographic separation was about 4 min. The method was validated for the concentration range 5–100 ng/ml. Mean recoveries were 98.0% for risperidone and 83.5% for 9-hydroxyrisperidone. Intra- and inter-day relative standard deviations were less than 11% for both compounds, while accuracy, expressed as percent error, ranged from 1.6 to 25%. The limit of quantitation was 2 ng/ml for both analytes. The method shows good specificity with respect to commonly prescribed psychotropic drugs, and it has successfully been applied for pharmacokinetic studies and therapeutic drug monitoring. 相似文献
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Antonio Rosato Leonardo Tenori Marta Cascante Pedro Ramon De Atauri Carulla Vitor A. P. Martins dos Santos Edoardo Saccenti 《Metabolomics : Official journal of the Metabolomic Society》2018,14(4):37
Introduction
Metabolomics is a well-established tool in systems biology, especially in the top–down approach. Metabolomics experiments often results in discovery studies that provide intriguing biological hypotheses but rarely offer mechanistic explanation of such findings. In this light, the interpretation of metabolomics data can be boosted by deploying systems biology approaches.Objectives
This review aims to provide an overview of systems biology approaches that are relevant to metabolomics and to discuss some successful applications of these methods.Methods
We review the most recent applications of systems biology tools in the field of metabolomics, such as network inference and analysis, metabolic modelling and pathways analysis.Results
We offer an ample overview of systems biology tools that can be applied to address metabolomics problems. The characteristics and application results of these tools are discussed also in a comparative manner.Conclusions
Systems biology-enhanced analysis of metabolomics data can provide insights into the molecular mechanisms originating the observed metabolic profiles and enhance the scientific impact of metabolomics studies.110.
Moreno Zolfo Francesco Asnicar Paolo Manghi Edoardo Pasolli Adrian Tett Nicola Segata 《Biology direct》2018,13(1):9