Parallel and multiplexed bead-based assays and encoding strategies

Advances in high throughput screening (HTS), together with the rapid progress in combinatorial chemistry, genomic and proteomic sciences have dramatically stimulated the development of a variety tools to enable the drug discovery process to become more efficient. Major future challenges in HTS include obtaining high density and good quality data based on assays that are rapid, reliable, inexpensive, sensitive, simple and miniaturised. This paper reviews the development and role of bead-based assays for HTS including DNA and single nucleotide polymorphism (SNP) assays, particularly from a multiplex perspective and evaluating the recent advances in bead-based arrays. The encoding strategies that are commonly used in bead-based assays are highlighted, while the importance of magnetic beads in genomic and proteomic purifications is discussed. In conclusion, bead-based assays offer a powerful promising approach for many aspects of drug discovery.     

Optical Properties of Model Compounds of Polyaniline

The UV and visible spectra of six model compounds were studied. These compounds can be considered as models of polyaniline in the reduced, cation radical, partially oxidized and oxidized forms. After treatment of a mixture of equal molar quantities of the reduced form (DPPD) and the oxidized form (QDIM) with acid, the following reaction was observed: DPPD(I)+QDIM(III)+2H⁺=2DPPD⁺(II) After similar treatment of the partially oxidized form (V) with acid, the radical cation salt formed. The UV and visible spectra of polyaniline in the reduced form, oxidized form and conductive form are similar to the spectra of DPPD, QDIM and DPPD⁺ or radical cation salt of V respectively. We propose that the polyaniline synthesized by chemical oxidation of aniline consists of oxidized and reduced repeat units. Upon protonation a redox reaction (or electron rearrangement) occurs and forms delocalized radical cations (polarons) in the polymer chain which are highly conductive.     

Solid Phase Synthesis of 4H-Pyrimido[2,1-b] Benzothiazol-4-ones from Resin-Bound Cyclic Malonic Ester

The solid phase synthesis of 4H-pyrimido[2,1-6] benzothizaol-4-ones has been reported.     

THE STRUCTURAL BASIS OF THE POOR FIBRIN SPECIFICITY OF UROKINASE(Ⅰ)——KNOWLEDGE-BASED PREDICTION OF KRINGLE STRUCTURES OF UROKINASE AND ITS RELATED PROTEINS

The Kringle-1 structure of plasminogen (PGK-1), the Kringle-2 structure of tissue plasminogen activator (PAK-2) and the Kringle structure of prourokinase (UKK) has been modeled on the basis of the three-dimensional structure of Kringle-1 of prothrombin (PTK-1) at 2.8 resolution. The predicted three-dimensional structure of these Kringles shows that the binding site of PGK-1 is characterized by an apparent dipolar site, the polar parts of which are separated by a hydrophobic region. PAK-2 possesses the anionic center but has not a cationic binding center which might be provided by a guanidinium group from Arg-69 located adjacent to the Arg-71 position. UKK possesses neither the anionic binding center nor the cationic center which are probably the main reason for the poor fibrin specificity of urokinase.     

Selenium speciation by coupling vesicle mediated HPLC with off-line ETAAS and on-line focused microwave digestion HG-AAS detection

A novel High Performance Liquid Chromatography (HPLC) method for the separation of selenium species with specific detection by off-line Electrothermal Atomization Atomic Absorption Spectrometry (ETAAS) or on-line focused microwave digestion (MW) Hydride Generation Atomic Absorption Spectrometry (HG-AAS) is described. Vesicular mobile phases of the cationic surfactant didodecyldimethylammonium bromide (DDAB) have been evaluated for the liquid chromatographic separation of inorganic selenium (selenite and selenate) and different selenoaminoacids (selenocystine, selenomethionine and selenoethionine) on a C(18) reversed-phase column modified by DDAB molecules. The effects of different parameters (pH, buffer and vesicle concentrations) of the mobile phase on the retention times have been determined. The detection limit for selenium with the proposed off-line HPLC-ETAAS method has been found to be 5 microg/L of Se. The detection limit using HPLC-"on line" focused microwave digestion-HG-AAS has been found to be 1 microg/L of Se, with a precision (repeatability) better than +/- 5%. The latter proved to be an exceptional on-line real-time chromatographic detector for selenium speciation purposes.     

Iron(III)-catalyzed Prins-type cyclization using homopropargylic alcohol: a method for the synthesis of 2-alkyl-4-halo-5,6-dihydro-2H-pyrans

[reaction: see text] A new Prins-type cyclization between homopropargylic alcohol and aldehydes in the presence of FeX(3) to obtain 2-alkyl-4-halo-5,6-dihydro-2H-pyrans in good yield is described. Osmium-catalyzed cis dihydroxylation provided direct access to trans-2-alkyl-3-hydroxy-tetrahydro-pyran-4-ones. Anhydrous ferric halides are also shown to be excellent catalysts for the standard Prins cyclization using homoallylic alcohol. Isolation of an intermediate acetal provides substantiation of a proposed mechanism.     

一种液晶环氧树脂固化中扩散控制动力学研究

根据扩散控制反应的基本原理 ,建立了合适的反应模型 ,描述了 4 ,4′ 二 ( 2 ,3 环氧丙氧基 )偶氮苯(DGEAP) / 4,4′ 二氨基二苯甲烷 (DDM)环氧树脂的固化行为 .该模型认为 ,随着环氧基团反应程度的提高 ,基团的反应半径将受到影响 .当体系中出现了介晶基元的有序排列时 ,与之相连的反应基团的分布也受到影响 ,有序区内的局部浓度将变大 ,产生假浓度效应 ,并最终影响扩散控制反应动力学 .通过与普通环氧树脂固化动力学的比较 ,证实了这一效应 .     

Synthesis of 4-aryl-2,3,6,7-tetrahydro-1H-pyrimido[4,5-b][1,4]-diazepin-6-ones from 4,5-diamino-1H-pyrimidin-6-ones and 1-aryl-3-(dimethylamino)-1-propanones

The reaction of 1-aryl-3-(dimethylamino)-1-propanones 1 with one equivalent of 4,5-diamino-1H-pyrimidin-6-ones 2 , in acidic medium, leads to the formation of 4-aryl-2,3,6,7-tetrahydro-1H-pyrimido[4,5-b]-[1,4]diazepin-6-ones 3 . The structure elucidation of the products is based on detail nmr analysis of experiments such as ¹³C, ¹H and DEPT including selective ¹³C{¹H} decoupling experiments.     

STUDIES ON cis-trans-ISOMERIZATION AND REACTION KINETICS OF A μ, η~2-VINYL LIGAND IN A TRIOSMIUM CLUSTER

The dihydride cluster H_2O_(s_3)(CO)_(10) reacts with ethyne to give a cis-adduct [O_(s_3)H(μ,η~2-CH=CH_2)(CO)_(10)]. The high deuterated cluster D_2O_(s_3)(CO)_(10), the reaction of D_2O_(s_3)(CO)_(10)with ethyne C_2H_2 to form the vinyl product cluster [O_(s_3)D(μ, η~2-CH=CHD)(CO)_(10)], and thereaction of H_2O_(s_3)(CO)_(10) with the deuterated ethyne C_2D_2 to form [O_(s_3)H(μ,η~2-CD=CDH)(CO)_(10)] have been reported primarily in this paper. The two cis-adducts undergo cis-trans-isomerization of μ,η~2-vinyl ligands under a small amount of the nucleophile pyridine. Usingthe combination of deuteration and dynamic ~1H,~2H NMR spectra, we report the experimen-tal evidence determined by the dynamic ~1H, ~2H NMR spectra, mechanism, and kinetic dataof the isomerization.     

Structural changes of the gold-support interface during CO oxidation catalyzed by mononuclear gold complexes bonded to zeolite NaY: evidence from time-resolved X-ray absorption spectroscopy

Mononuclear gold complexes synthesized from AuIII(CH3)2(acac) in zeolite NaY were characterized by time-resolved X-ray absorption spectroscopy and infrared spectroscopy as they catalyzed CO oxidation at 298 K and 760 Torr in flow systems. Initial contact with a CO + O2 mixture led to the rapid formation of cationic gold complexes in which Au was bonded to approximately two zeolite O atoms, on average. Further contact with CO + O2 led to breaking of an Au-surface oxygen bond, giving a gold carbonyl anchored to approximately one O atom. The process was reversed in the absence of CO and O2.