Oxidative and hydrolytic DNA cleavage by Cu(II) complexes of salicylidene tyrosine schiff base and 1,10 phenanthroline/bipyridine

Ternary Cu(II) complexes [Cu(II)(saltyr)(B)] (1,2), (saltyr = salicylidene tyrosine, B = 1,10 phenanthroline (1) or 2,2′ bipyridine (2)) were synthesized and characterized by various techniques. The complexes exhibit square pyramidal (CuN₃O₂) geometry. CT-DNA binding studies revealed that the complexes show good binding propensity (K_b = 3.47 × 10⁴ M⁻¹ and 3.01 × 10⁴ M⁻¹ for 1 and 2, respectively). The role of these complexes in the oxidative and hydrolytic DNA cleavage was studied. The catalytic ability of 1 and 2 follows the order: 1 > 2. The rate constants for the hydrolysis of phosphodiester bond were determined as 2.80 h⁻¹ and 2.11 h⁻¹ for 1 and 2, respectively. It amounts to (0.58-0.77) × 10⁸ fold rate enhancement compared to non-catalyzed DNA cleavage, which is significant.     

嘧啶类酪氨酸激酶抑制剂

酪氨酸激酶在肿瘤的发生、发展过程中起着非常重要的作用,已成为肿瘤治疗的新靶点.嘧啶类化合物是蛋白酪氨酸酶抑制剂(PTKIs)中的一大类,这类化合物在临床前期研究中显示具有很好的抗肿瘤效应,一些已在临床上作为很有前景的抗癌药.本文按其结构类别介绍了近年来报道的嘧啶类酪氨酸激酶抑制剂.     

In situ copper oxide modified molecularly imprinted polypyrrole film based voltammetric sensor for selective recognition of tyrosine

Organic-inorganic hybrids are promising functional materials as they combine the special characteristics of both organic (polymer) and inorganic phases. Among different existing approaches for the preparation of such polymer-inorganic hybrid coatings, in situ electrochemical methods are very advantageous because of their high sensitivity and simplicity. In the present study, voltammetric sensors for tyrosine are designed and developed via various modifications on glassy carbon electrode such as polypyrrole coated GCE, molecularly imprinted polypyrrole coated GCE (MIPPy) and in situ copper oxide modified MIPPy coated GCE. Of these, in situ copper oxide modified MIPPy coated GCE sensor responds to tyrosine concentrations in the range 1 × 10⁻⁸ to 1 × 10⁻⁶ and 2 × 10⁻⁶ to 8 × 10⁻⁶ M with a very low detection limit of 4.0 × 10⁻⁹ M and by far the most sensitive one. Detailed linear sweep voltammetric and chronoamperometric experiments were undertaken to investigate the electrocatalytic behavior of tyrosine. The electron transfer coefficient, diffusion coefficient and charge transfer rate constants involved in the sensing process using in situ copper oxide modified MIPPy film coated GCE are 0.47, 1.88 × 10⁻⁶ cm² s⁻¹, 4.7 × 10⁶ L mol⁻¹ s⁻¹, respectively. Furthermore, the designed sensor is highly selective and has been applied successfully for the analysis of synthetic and real samples of human urine.     

Development of a microchip‐pulsed electrochemical method for rapid determination of L‐DOPA and tyrosine in Mucuna pruriens

L ‐3,4‐dihydroxyphenylalanine (L‐DOPA) is a well‐recognized therapeutic compound to Parkinson's disease. Tyrosine is a precursor for the biosynthesis of L‐DOPA, both of which are widely found in traditional medicinal material, Mucuna pruriens. In this paper, we described a validated novel analytical method based on microchip capillary electrophoresis with pulsed electrochemical detection for the simultaneous measurement of L‐DOPA and tyrosine in M. pruriens. This protocol adopted end‐channel amperometric detection using platinum disk electrode on a homemade glass/polydimethylsiloxane electrophoresis microchip. The background buffer consisted of 10 mM borate (pH 9.5) and 0.02 mM cetyltrimethylammonium bromide, which can produce an effective resolution for the two analytes. In the optimal condition, sufficient electrophoretic separation and sensitive detection for the target analytes can be realized within 60 s. Both tyrosine and L‐DOPA yielded linear response in the concentration range of 5.0–400 μM (R² > 0.99), and the LOD were 0.79 and 1.1 μM, respectively. The accuracy and precision of the established method were favorable. The present method shows several merits such as facile apparatus, high speed, low cost and minimal pollution, and provides a means for the pharmacologically active ingredients assay in M. pruriens.     

Construction of europium hexacyanoferrate film and its electrocatalytic activity to tyrosine determination

In this work, a rare-earth metal hexacyanoferrate film, europium hexacyanoferrate film, was electrodeposited on the graphite electrode. For the first time, XPS was employed to confirm that the valences of Fe in the film were changed during the electrochemical reaction, and proper electrochemical equations were proposed. Then, the electrochemical characterization of the film, such as film thickness, the number of electrons, and the apparent heterogeneous electron transfer rate constant, was deduced from cyclic voltammograms. Furthermore, this film was found to exhibit an electrocatalytic activity to the oxidation of tyrosine. The experimental conditions, pH value and the applied potential, are investigated in detail. At the optimal conditions, the electrocatalytic response is a linear relationship with the concentration of tyrosine in the range of 10 μM and 0.6 mM, with a detection limit of about 8 μM.     

Microcalorimetric Study on Tyrosine Oxidation Catalyzed by Tyrosinase

At present, several methods are available for kinetic studies of enzyme-catalyzed reactions, but study on the reaction of Pseudomonas maltophilia tyrosiase by microcalorimetry has not been reported yet. Tyrosinase, ecoded by mel gene, is copper-containing enzyme, which can catalyze and oxidize tyrosine L-dopa to melanin. It exists in the organism of fungi, actinomycetes, bacteria, gymnosperms, angiosperms, insects, chordata, mammals, and human etc.. Tyrosinase from different source has differ…     

Gold nanoparticle-based electrochemical detection of protein phosphorylation

In this report, we demonstrate the application of Au nanoparticles in the electrochemical detection of protein phosphorylation. The method is based on the labeling of a specific phosphorylation event with Au nanoparticles, followed by electrochemical detection. The phosphorylation reaction is coupled with the biotinylation of the kinase substrate using a biotin-modified adenosine 5′-triphosphate [γ]-biotinyl-3,6,9-trioxaundecanediamine (ATP) as the co-substrate. When the phosphorylated and biotinylated kinase substrate is exposed to streptavidin-coated Au nanoparticles, the high affinity between the streptavidin and biotin resulted in the attachment of Au nanoparticles on the kinase substrate. The electrochemical response obtained from Au nanoparticles enables monitoring the activity of the kinase and its substrate, as well as the inhibition of small molecule inhibitors on protein phosphorylation. We determined the activity of Src non-receptor protein tyrosine kinase, p60^c-Src and protein kinase A in combination with their highly specific substrate peptides Raytide™ EL and Kemptide, respectively. The detection limits for Raytide™ EL and Kemptide were determined as 5 and 10 μM, (S/N = 3), and the detection limits for the kinase activity of p60^c-Src and protein kinase A (PKA) were determined as 5 and 10 U mL⁻¹, (S/N = 3), respectively. Tyrosine kinase reactions were also performed in the presence of a well-defined inhibitor, 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d]pyrimidine (PP2), and its negative control molecule, 4-amino-7-phenylpyrazol[3,4-d] pyrimidine (PP3), which had no inhibition effect. Based on the dependency of Au nanoparticle signal on inhibitor concentration, IC₅₀ value, half-maximal inhibition of the inhibitors was estimated. IC₅₀ values of PP2, genistein and herbimycin A to p60^c-Src were detected as 5 nM, 25 μM and 900 nM, respectively. The inhibition of PKA activity on Kemptide using ellagic acid was monitored with an IC₅₀ of 3.5 μM. The performance of the biosensor was optimized including the kinase reaction, incubation with streptavidin-coated Au nanoparticles, and the small molecule inhibitors. Kinase peptide-modified electrochemical biosensors are promising candidates for cost-effective kinase activity and inhibitor screening assays.     

Fast quantitative analysis of four tyrosine kinase inhibitors in different human plasma samples using three‐way calibration‐ assisted liquid chromatography with diode array detection

A simple method has been developed by combining high‐performance liquid chromatography with diode array detection with the alternating trilinear decomposition method for simultaneous determination of four tyrosine kinase inhibitors in different human plasma samples. Chromatographic separation of the analytes was performed on a reversed‐phase column with methanol (65%, v/v, A) and 0.1% aqueous solution of formic acid (35%, v/v, B). Analysis time was 5.0 min per run and analytes could be completely eluted within 2.8??3.8 min. The calibration concentration ranges of vandetanib, pazopanib, afatinib and dasatinib were designed as 0.50–6.10, 0.50–6.10, 0.70–7.00 and 0.70–7.00 μg·mL^?1, respectively. The intra‐ and inter‐day RSDs ranged between 0.1 and 8.9%. Quantitative information could be extracted from the unsegregated interferences of different human plasma samples with the aid of the “second‐order advantage” of three‐way (second‐order) calibration methods. All results demonstrated that the proposed method for direct quantitative analysis of four tyrosine kinase inhibitors in different complex systems possessed good characteristics of rapidity, sensitivity and efficiency, and it is expected to be an attractive choice in the fast analysis of clinical samples.     

酪氨酸与1-亚硝基-2-萘酚反应的研究

本文用荧光、分子吸收光谱和电化学等方法研究了在含 Na NO2 的 HNO3溶液中酪氨酸与 1 -亚硝基 - 2 -萘酚的反应 ,该反应最后生成具有荧光性质的酚噻嗪类化合物。于 - 0 .5 3V( vs. SCE)处被还原的反应中间物酚噻嗪类化合物的氧化物可被光还原为酚噻嗪类化合物 ,其分解过程的反应为二级反应 ;反应速度常数为 5× 1 0 - 4L· mol- 1· min- 1。酚噻嗪类化合物的生成过程为一级反应 ,反应速度常数为 0 .0 2 1min     

Preparation, characterization and surface morphology of novel optically active poly(ester-amide)/functionalized ZnO bionanocomposites via ultrasonication assisted process

Novel bionanocompoites (BNCs) were prepared using zinc oxide (ZnO) nanoparticles which functionalized by γ-methacryloxypropyltrimethoxysilane (KH570) as a coupling agent. Poly(ester-amide) (PEA) based on tyrosine natural amino acid was synthesized and used as a polymer matrix. PEA/ZnO BNCs were characterized by fourier transform infrared spectra (FT-IR), X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM) and transmission electron microscopy (TEM). All the results confirmed that the surface of ZnO particle has sufficient compatibility with PEA through the link of the coupling agent between ZnO and polymer and also proved that the presence of ZnO nanoparticles appeared to be dispersed in nanosize in polymer composite matrix. In addition, thermogravimetric analysis (TGA) data indicated an enhancement of thermal stability of new BNC materials compared with the pure polymer.