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81.
This paper provides analytical chemical information on selected new molecular entities (NMEs) which are drugs that have recently been approved by the FDA. These are the antiretroviral drugs, atazanavir, indinavir and emtricitabine, the antibacterial gemifloxacin, rosuvastatine which is a cholesterol-lowing drug, the anti-cancer drug gefitinib and aprepitant for neurological disorders. Electrospray ionisation-quadrupole ion trap mass spectrometry (ESI-MSn) was employed to generate tandem mass spectrometric (MS2) data of the drugs studied and structural assignments of product ions were supported by quadrupole time-of-flight mass spectrometry (QToF-MS/MS). These fragmentation studies were then utilised in the development and validation of a specific and sensitive liquid chromatographic method (LC–ESI-MS2) to identify and determine these drugs at therapeutic concentration levels in serum after a single protein precipitation procedure with acetonitrile. In addition, this method was compared to the application of gas liquid chromatography-flame ionisation detection (GLC-FID) and differential pulse polarography (DPP) for the analysis of these NMEs in serum. 相似文献
82.
Radiation Damage and Racemic Protein Crystallography Reveal the Unique Structure of the GASA/Snakin Protein Superfamily 下载免费PDF全文
Ho Yeung Dr. Christopher J. Squire Yuliana Yosaatmadja Dr. Santosh Panjikar Gemma López Prof. Dr. Antonio Molina Prof. Dr. Edward N. Baker Dr. Paul W. R. Harris Prof. Dr. Margaret A. Brimble 《Angewandte Chemie (International ed. in English)》2016,55(28):7930-7933
Proteins from the GASA/snakin superfamily are common in plant proteomes and have diverse functions, including hormonal crosstalk, development, and defense. One 63‐residue member of this family, snakin‐1, an antimicrobial protein from potatoes, has previously been chemically synthesized in a fully active form. Herein the 1.5 Å structure of snakin‐1, determined by a novel combination of racemic protein crystallization and radiation‐damage‐induced phasing (RIP), is reported. Racemic crystals of snakin‐1 and quasi‐racemic crystals incorporating an unnatural 4‐iodophenylalanine residue were prepared from chemically synthesized d ‐ and l ‐proteins. Breakage of the C?I bonds in the quasi‐racemic crystals facilitated structure determination by RIP. The crystal structure reveals a unique protein fold with six disulfide crosslinks, presenting a distinct electrostatic surface that may target the protein to microbial cell surfaces. 相似文献
83.
Enantioselective Generation of Adjacent Stereocenters in a Copper‐Catalyzed Three‐Component Coupling of Imines,Allenes, and Diboranes 下载免费PDF全文
Kay Yeung Rebecca E. Ruscoe Dr. James Rae Dr. Alexander P. Pulis Prof. Dr. David J. Procter 《Angewandte Chemie (International ed. in English)》2016,55(39):11912-11916
A highly enantio‐ and diastereoselective copper‐catalyzed three‐component coupling affords the first general synthesis of homoallylic amines bearing adjacent stereocenters from achiral starting materials. The method utilizes a commercially available NHC ligand and copper source, operates at ambient temperature, couples readily available simple imines, allenes, and diboranes, and yields high‐value homoallylic amines that exhibit versatile amino, alkenyl, and boryl units. 相似文献
84.
Enzymatic Synthesis of Sequence‐Defined Synthetic Nucleic Acid Polymers with Diverse Functional Groups 下载免费PDF全文
Dehui Kong Yi Lei Wayland Yeung Prof. Ryan Hili 《Angewandte Chemie (International ed. in English)》2016,55(42):13164-13168
The development and in‐depth analysis of T4 DNA ligase‐catalyzed DNA templated oligonucleotide polymerization toward the generation of diversely functionalized nucleic acid polymers is described. The NNNNT codon set enables low codon bias, high fidelity, and high efficiency for the polymerization of ANNNN libraries comprising various functional groups. The robustness of the method was highlighted in the copolymerization of a 256‐membered ANNNN library comprising 16 sub‐libraries modified with different functional groups. This enabled the generation of diversely functionalized synthetic nucleic acid polymer libraries with 93.8 % fidelity. This process should find ready application in DNA nanotechnology, DNA computing, and in vitro evolution of functional nucleic acid polymers. 相似文献
85.
Cover Picture: Radiation Damage and Racemic Protein Crystallography Reveal the Unique Structure of the GASA/Snakin Protein Superfamily (Angew. Chem. Int. Ed. 28/2016) 下载免费PDF全文
86.
87.
Yeung CK Sommerhage F Wrobel G Offenhäusser A Chan M Ingebrandt S 《Analytical and bioanalytical chemistry》2007,387(8):2673-2680
Microelectrode arrays (MEAs) with evenly distributed multiple sensor spots have been designed for specific applications. Using the MEAs, we determined the relative profiles of potassium channel openers (KCOs) on cultured embryonic Sprague-Dawley rat cardiac myocytes. KCO, pinacidil (PIN), cromakalim (CROM), SDZ PCO400 (SDZ), or its vehicle, was added to the myocytes cumulatively. The action potential signal shapes in the presence of PIN and SDZ show that the changes in voltage over time and the magnitudes of the associated voltage change were reduced concentration-dependently. CROM affected sodium influx more than PIN and SDZ. The comparisons of changes in the rate of beating and propagation speed in the presence of KCOs were made using their corresponding pD(2) values (the negative log of EC(50)). All KCOs caused concentration-dependent reductions in the rate of beating and propagation speed, with SDZ being the most potent. In addition to the signal shapes, rate of beating, and propagation speed, the origin of excitation and the excitation pattern inside the culture can be also extracted. The results show that the present system can differentiate the effects of different KCOs on myocytes. It might be possible to utilise the MEA as a means to classify drug action based upon a combined interpretation of the three different datasets gained from the extracellular recordings. The combination of these observations might be used as 'drug signatures' when profiling drugs in the future. 相似文献
88.
Kou X Zhang S Tsung CK Yang Z Yeung MH Stucky GD Sun L Wang J Yan C 《Chemistry (Weinheim an der Bergstrasse, Germany)》2007,13(10):2929-2936
Gold nanorods were prepared in high yields by using a one-step seed-mediated process in aqueous cetyltripropylammonium bromide (CTPAB) and cetyltributylammonium bromide (CTBAB) solutions in the presence of silver nitrate. The diameters of the nanorods range from 3 to 11 nm, their lengths are in the range of 15 to 350 nm, and their aspect ratios are in the range of 2 to 70. The diameters of the Au nanorods obtained from one growth batch in CTPAB solutions decrease as their lengths increase, and their volumes decrease as the aspect ratios increase. The diameters of the Au nanorods obtained from one growth batch in CTBAB solutions first decrease and then slightly increase as their lengths increase, and their volumes increase as the aspect ratios increase. These Au nanorods are single-crystalline and are seen to be oriented in either the [100] or [110] direction under transmission electron microscopy imaging, irrespective of their sizes. To the best of our knowledge, this is the first report of the preparation by using wet-chemistry methods of single-crystalline Au nanorods with aspect ratios larger than 15. 相似文献
89.
We applied total internal reflection fluorescence microscopy (TIRFM) to study intermolecular interactions at the water/fused-silica interface at the single-molecule level. Real-time molecular motion at the interface was recorded to reveal adsorption behavior and conformational dynamics of three DNAs with sticky ends of different numbers of unpaired bases. Features of DNA motion at the interface, such as evanescent-field residence time, linear velocity and frequency of adsorption/desorption events were measured to assess the relative affinities of the oligonucleotides for the surface. The general trend of stronger interaction with the surface for longer sticky ends confirmed hydrophobic interaction and hydrogen bonding as the driving forces of DNA adsorption to fused-silica at pH 5. For DNAs of different sizes, different conformational dynamics and the accessibility of sticky ends give rise to a nonlinear relationship with respect to affinity. Such information may prove valuable for chromatography studies as well as for the design of DNA microarrays and drug delivery systems. 相似文献
90.
亲和毛细管电泳激光诱导荧光法测定牛血清白蛋白与其单克隆抗体的结合常数 总被引:5,自引:0,他引:5
生物分子之间的特异性相互作用是生物界普遍存在的现象.研究这些现象,对揭示生物化学作用机理、药物研究等具有重要意义.结合常数Kb是描述生物分子之间特异性相互作用最主要的参数,测定结合常数的传统方法包括平衡透析、凝胶过滤色谱和分光光度法等[1].亲和毛细管电泳(Affinitycapillaryelectrophoresis,简称ACE)是近几年发展起来的毛细管电泳的一个分支,在研究生物分子之间特异性相互作用等方面有很好的应用前景[2~5].与上述传统方法相比,ACE具有测定速度快,样品用量少,有多… 相似文献