A new way to increase performance of oxide electrode for oxygen reduction using grain growth inhibitor

Nickel oxide was introduced as a grain growth inhibitor into Ba_0.5Sr_0.5Co_0.8Fe_0.2O_3 − δ (BSCF) electrode to increase its activity for oxygen reduction reaction. Small amount of NiO can effectively suppress the grain growth of BSCF by spinning the grain boundary and thus increase the electrode surface area, while the particle connection is not obviously affected. Electrochemical impedance spectra of symmetric cells indicate that the electrode activity for oxygen reduction is indeed effectively improved by introducing NiO additive. At 600 °C, area specific resistance of BSCF+5wt.% NiO is about 36.5% lower than that of pure BSCF electrode. Single cell tests also demonstrate an improved cell power output by introducing NiO additive. It implies that the adoption of a sintering inhibitor may be a facile and practical way to increase electrode activity for oxygen reduction.     

铜表面腐蚀的激光扫描微区光电压图象的研究

铜表面腐蚀的激光扫描微区光电压图象的研究杨迈之，张雯，蔡生民，任聚杰（北京大学化学系，北京，１０００７１）（河北医学院化学系，石家庄）潘传智，杨勇（浙江工业大学化工系，杭州）（厦门大学化学系，厦门）关键词铜，缓蚀剂，微区光电压图铜的腐蚀与防腐早已引起...     

Quantitation of unbound sunitinib and its metabolite N-desethyl sunitinib (SU12662) in human plasma by equilibrium dialysis and liquid chromatography-tandem mass spectrometry: application to a pharmacokinetic study

A rapid, selective, and sensitive liquid chromatography–tandem mass spectrometry method was developed and validated for the simultaneous determination of unbound sunitinib and its active metabolite N‐desethyl sunitinib in plasma. Plasma and post‐dialysis buffer samples were extracted using a liquid–liquid extraction procedure with acetonitrile–n‐butylchloride (1:4, v/v). Chromatographic separation was achieved on a Waters X‐Terra® MS RP₁₈ column with a mobile phase consisting of acetonitrile and water (60:40, v/v) containing formic acid (0.1%, v/v) using an isocratic run, at a flow‐rate of 0.2 mL/min. Analytes were detected by electrospray tandem mass spectrometry in the selective reaction monitoring mode. Linear calibration curves were generated over the ranges 0.1–100 and 0.02–5 ng/mL for sunitinib and 0.2–200 and 0.04–10 ng/mL for N‐desethyl sunitinib in plasma and in phosphate‐buffered solution, respectively. The values for both within‐day and between‐day precision and accuracy were well within the generally accepted criteria for analytical methods. The analytical range was sufficient to determine the unbound and total concentrations of both analytes. The method was applied for measurement unbound concentrations in addition to total concentrations of sunitinib and its metabolite in plasma of a cancer patient receiving 50 mg daily dose. Copyright © 2012 John Wiley & Sons, Ltd.     

Gold nanoparticle-enhanced surface plasmon resonance measurement with a highly sensitive quantification for human tissue inhibitor of metalloproteinases-2

Two different methods for the quantification of human tissue inhibitor of metalloproteinases-2 (TIMP-2) were developed using surface plasmon resonance (SPR) and gold nanoparticles for signal enhancement. The first method, a competitive assay, used TIMP-2 immobilized to the sensor surface and the inactive form of matrix metalloproteinase-2 (proMMP-2) (EC 3.4.24.24) adsorbed to gold nanoparticles. The sensor signals resulting from the interaction of MMP-2-gold nanoparticles with immobilized TIMP-2 were inversely proportional to the amounts of TIMP-2 of the sample. The measuring range for TIMP-2 was about 15–180 pM. The second method, a one-step sandwich assay, used proMMP-2 immobilized to the sensor surface and an anti-TIMP-2 monoclonal antibody coupled to gold nanoparticles. The lower detection limit of this assay format was 0.5 pM of TIMP-2. The binding signals were highly reproducible up to 100 pM of the inhibitor. The improvements obtained in TIMP-2 quantification over already existing tests could contribute to a better understanding and diagnosis of diseases like cancer.     

Downfalls of Chemical Probes Acting at the Kinase ATP-Site: CK2 as a Case Study

Protein kinases are a large class of enzymes with numerous biological roles and many have been implicated in a vast array of diseases, including cancer and the novel coronavirus infection COVID-19. Thus, the development of chemical probes to selectively target each kinase is of great interest. Inhibition of protein kinases with ATP-competitive inhibitors has historically been the most widely used method. However, due to the highly conserved structures of ATP-sites, the identification of truly selective chemical probes is challenging. In this review, we use the Ser/Thr kinase CK2 as an example to highlight the historical challenges in effective and selective chemical probe development, alongside recent advances in the field and alternative strategies aiming to overcome these problems. The methods utilised for CK2 can be applied to an array of protein kinases to aid in the discovery of chemical probes to further understand each kinase’s biology, with wide-reaching implications for drug development.     

Protease Inhibitors Purified from the Canola Meal Extracts of Two Genetically Diverse Genotypes Exhibit Antidiabetic and Antihypertension Properties

Valorization of vegetable oil waste residues is gaining importance due to their high protein and polyphenol contents. Protease inhibitors (PIs), proteins from these abundantly available waste residues, have recently gained importance in treating chronic diseases. This research aimed to use canola meal of genetically diverse Brassica napus genotypes, BLN-3347 and Rivette, to identify PIs with diverse functionalities in therapeutic and pharmacological applications. The canola meal PI purification steps involved: native PAGE and trypsin inhibition activity, followed by ammonium sulfate fractionation, anion exchange, gel filtration, and reverse-phase chromatography. The purified PI preparations were characterized using SDS-PAGE, isoelectric focusing (IEF), and N terminal sequencing. SDS-PAGE analysis of PI preparations under native reducing and nonreducing conditions revealed three polymorphic PIs in each genotype. The corresponding IEF of the genotype BLN-3347, exhibited three acidic isoforms with isoelectric points (pI) of 4.6, 4.0, and 3.9, while Rivette possessed three isoforms, exhibiting two basic forms of pI 8.65 and 9.9, and one acidic of pI 6.55. Purified PI preparations from both the genotypes displayed dipeptidyl peptidase-IV (DPP-IV) and angiotensin-converting enzyme (ACE) inhibition activities; the BLN-3347 PI preparation exhibited a strong inhibitory effect with lower IC₅₀ values (DPP-IV 37.42 µg/mL; ACE 129 µg/mL) than that from Rivette (DPP-IV 67.97 µg/mL; ACE 376.2 µg/mL). In addition to potential human therapy, these highly polymorphic PIs, which can inhibit damaging serine proteases secreted by canola plant pathogens, have the potential to be used by canola plant breeders to seek qualitative trait locus (QTLs) linked to genes conferring resistance to canola diseases.     

新型喹唑啉类PDE7抑制剂类似物的合成

以邻氨基苯甲酸为原料,经溴代和环合反应合成了4个新型喹唑啉类PDE7抑制剂类似物,其结构经1H NMR和ESI-MS表征。     

细管电泳-激光诱导荧光检测用于多个胞内蛋白激酶的抑制剂筛选和选择性评价

发展了一种基于毛细管电泳(CE)-激光诱导荧光(LIF)检测的多个细胞内源激酶的抑制剂平行筛选及选择性评价方法。CE高效的分离能力和LIF检测器的高选择性,使得同时测试多个胞内激酶的活性成为可能。共4种细胞系、3种特异性蛋白激酶底物肽、2种选择性蛋白激酶抑制剂和1种非选择性蛋白激酶抑制剂用于方法的建立。特异性底物肽与细胞裂解液混合后孵育,被其相应的激酶选择性地磷酸化,利用CE-LIF分离检测磷酸化产物和底物肽。同时测定一个抑制剂对几种蛋白激酶的抑制活性,用于评价抑制剂的选择性。与传统的单靶标筛选模式相比,这种基于细胞裂解液的多靶标筛选方法能提供更多的信息,更加高效,且细胞裂解液作为一种廉价的激酶来源大大降低了筛选成本。     

含乙酰氧肟酸配体的席夫碱钒配合物的合成、结构及其抑制幽门螺旋杆菌脲酶研究

本文合成了2个新的含乙酰氧肟酸配体的席夫碱钒配合物,[V^ⅢL¹(HAHA)](1)和[V^ⅤOL²(AHA)](2),其中L¹为N,N’-二(5-甲基水杨基)乙烷-1,2-二胺的二价阴离子,L²为2-{[2-(2-羟乙基氨基)乙亚胺基]甲基}-6-甲基苯酚的一价阴离子,HAHA和AHA分别为乙酰氧肟酸的一价和二价阴离子,通过物理-化学方法以及单晶X-射线衍射表征了它们的结构。在每个化合物中,V原子都采取八面体配位构型。本文还研究了配合物的热稳定性以及其对幽门螺旋杆菌脲酶的抑制活性。在浓度为100μmol·L^-1时,配合物1和2对脲酶的抑制率分别为37.2%和81.5%,其中配合物2的IC₅₀值为21.5μmol·L^-1。分子对接研究表明配合物2与脲酶活性中心存在有效的作用力。     

Mapping the Active Site of the Bacterial Enzyme LpxC Using Novel Carbohydrate‐Based Hydroxamic Acid Inhibitors*

LpxC (UDP‐3‐O‐(R‐3‐hydroxymyristoyl)‐GlcNAc deacetylase), an enzyme involved in the biosynthesis of lipid A, is crucial for the growth of Gram‐negative bacteria. This enzyme has accordingly been identified as a potential target for the development of novel antibiotics against Gram‐negative bacteria. The carbohydrate‐derived hydroxamic acid 1 (1,5‐anhydro‐2‐C‐(carboxymethyl N‐hydroxyamide)‐2‐deoxy‐3‐O‐myristoyl‐ D‐glucitol) was previously shown to exhibit a wide spectrum of inhibitory activity against LpxC enzymes. Here we describe the preparation of seven analogs of 1 and their enzymatic evaluation. Two of the hydroxyl groups (OH‐3 and 6) of the GlcNAc residue were found to be involved in the binding interaction, and there is an important hydrophobic interaction in the vicinity O‐3 position with the enzyme that recognizes aromatic as well as aliphatic substituents.