Application of capillary zone electrophoresis to the study of interactions betweenBacillus subtilis tryptophanyl-tRNA synthetase and tRNATrp

Summary The application of capillary zone electrophoresis to the study of interactions betweenBacillus subtilis tryptophanyl-tRNA synthetase (TrpRS) and tRNA^Trp is described. Significant changes in peak shape of tRNA^Trp incubated with TrpRS indicated the occurrence of interactions between TrpRS and tRNA^Trp in pH 8.0 Tris-HCl buffer containing 0.1 mmol L⁻¹ EDTA and 1 mmol L⁻¹−5 mmol L⁻¹ mgCl₂. Addition of Mg²⁺ decreased the electrophoretic mobility of tRNA^Trp, which illustrated that conformation of tRNA^Trp depended on Mg²⁺. The dissociation constant of the TrpRS-tRNA^Trp complex was estimated to be 0.63 μmol L⁻¹ at 25°C in buffer solution.     

In silico based virtual screening and mixed mode QM/MM calculation identifies caffeine scaffold for designing potential inhibitors for tyrosyl tRNA synthetase of Mycobacterium tuberculosis

Aminoacyl tRNA synthetases are novel antibacterial drug target because of their important role in protein synthesis. In this study, we performed high throughput virtual screening of 205883 compounds from Asinex ligand database to identify potential specific inhibitors for Tyrosyl tRNA synthetase of Mycobacterium tuberculosis (MtbTyrRS). Compounds are ranked based on the glide extra precision docking score. It is noted that the top ranked compounds have caffeine scaffold. The top five caffeine analogs are further evaluated for other drug‐like properties. The binding energies of caffeine analogs are estimated using mixed mode quantum mechanics/molecular mechanics calculation. The results show that these caffeine analogs have good absorption, distribution, metabolism, and excretion properties and high binding affinity to the MtbTyrRS. This suggests that caffeine could be a new scaffold for designing inhibitors against Tyrosyl tRNA synthetase of M. tuberculosis. The top five caffeine analogs are also subjected to docking calculations with human cytosolic and mitochondrial Tyrosyl tRNA synthetases to ascertain their specificities toward MtbTyrRS. The comparative docking studies indicate that the top five caffeine analogs are specific for MtbTyrRS. © 2014 Wiley Periodicals, Inc.     

益生菌联合谷氨酰胺的肠内营养对重症急性胰腺炎肠黏膜屏障恢复的作用

目的研究了益生菌联合谷氨酰胺的肠内营养治疗对恢复重症急性胰腺炎（SAP）的肠道屏障功能的作用。方法将74例重症急性胰腺炎患者随机分为3组：常规肠内营养组（EN组）,肠内营养＋谷氨酰胺组（Gln组）,肠内营养＋谷氨酰胺＋益生菌制剂组（益生菌组）。治疗第1、7、14、21天进行APACHEⅡ评分,并取血测定血清中的谷氨酰胺、内毒素、CRP、D-乳酸水平。结果三组病人APACHE11评分、CRP均逐渐下降,在第7天,Gln组和益生菌组CRP水平下降,并且与EN组对比,差异有统计学意义,而益生菌组和Gln组在第14天的APACHEⅡ评分与EN组差异有统计学意义。三组患者血清Gln浓度在第7天测定均成不同程度下降,Gln组与益生菌组分别与EN组比较,差异无统计学意义。在第14天,三组Gln水平均上升,益生菌组与EN组对比,差异有统计学意义（P〈0.05）。在第7天,益生菌组的血清内毒素、D-乳酸水平低于EN组,差异有统计学意义。在第14天,Gln组和益生菌组的内毒素水平和D-乳酸水平均低于EN组,差异有统计学意义,益生菌组的DAO水平低于EN组,差异有统计学意义（P〈0.05）。结论应用益生菌制剂和Gln的肠内营养能更好地维护肠道黏膜屏障的完整,应用前景广阔。但益生菌制剂和Gln免疫制剂问的协同作用需要进一步论证。     

2-[邻-4,6-二甲氧基嘧啶基-2-氧(硫)代苯基]-1,3,4-噻(噁)二唑类化合物的合成及其除草活性

以取代的邻硝基苯甲醛或水杨醛或邻巯基苯腈为原料,通过几步反应合成得到2-[邻-4,6-二甲氧基嘧啶-2-基-氧(硫)代苯基]-1,3,4-噻(噁)二唑类化合物.初步田间试验证实,30%化合物Ib乳油的使用剂量为2.40～3.60L·hm-2,对试验棉田杂草防除效果达48d,且对棉花较为安全.目标化合物的结构经过1H NMR,MS-ESI,IR以及元素分析等表征.     

Synthesis and Herbicidal Activity of Novel Sulfonylureas Containing 1,2,4-Triazolinone Moiety

A series of new sulfonylureas incorporating 1,2,4-triazolinone moiety was synthesized, which were further bio-assayed for the herbicidal activity against four herbs, representative of monocotyledons and dicotyledons. Some of them exhibited high potency to inhibit the growth of dicotyledons(Bassica napus and Amaranthus retroflexus) in the pot experiment. Compounds 9a and 9b also displayed an excellent herbicidal activity against Bassica napus at a concentration of 15 g/hectare, which were comparable with commercial triasulfuron.     

不同氮源对水稻幼苗根氨同化酶的影响

将氮索含量相同、但来源不同的氮源分别加入到水稻培养液中,分析了不同氮源对水稻幼苗根氨同化酶活性的影响．与无氮培养的水稻根相比,(NH4)zSO4,NH4NO3,KNO3,谷氨酸(Glu)和谷氨酰胺(Gin)都能分别促进水稻根谷氨酰胺合成酶(GS)、依赖于NADH的谷氨酸合酶(NADH-GOGAT)和依赖于NADH的谷氨酸脱氢酶(NADH-GDH)活性．(NH4)2SO．对GS和NADH-GOGAT活性促进最为显著,而Gln对GS和Glu对NADH-GOGAT的活性分别影响最小．Glu对NADH-GDH活性的诱导稍强于其它氮源．这些结果提示,不同氮源对水稻根氨同化酶活性影响的差别也许反映了这些物质对水稻根部氮索代谢的影响以及对这些酶诱导能力的不同．     

Reversible,Thermally Induced Domain Unfolding in Oligomeric Proteins. Spectral and DSC measurements

Spectral and differential scanning calorimetry (DSC) results for three oligomeric proteins are briefly reviewed. (A) Reversible, thermally-induced partial unfolding reactions in dodecameric glutamine synthetase from E. coli involve cooperative, two two-state transitions of subunits and demonstrate communication among subunits. (B) Thermal unfolding of intact Acanthamoeba myosin II is more cooperative than that of mammalian skeletal muscle myosin. Nucleotide-induced conformational changes thermally stabilize head domains in both myosins. The long dimeric coiled-coil rod of Acanthamoeba myosin II undergoes a reversible, cooperative, single two-state thermal transition with concomitant chain dissociation. (C) The amino terminal domain of enzyme I of the E. coliPEP:sugar phosphotransferase system is destabilized by phosphorylation of the active-site His 189. This revised version was published online in July 2006 with corrections to the Cover Date.     

In silico identification of potential inhibitors against human 2’-5’- oligoadenylate synthetase (OAS) proteins

As part of the type I IFN signaling, the 2′-5′- oligoadenylate synthetase (OAS) proteins have been involved in the progression of several non-viral diseases. Notably, OAS has been correlated with immune-modulatory functions that promote chronic inflammatory conditions, autoimmune disorders, cancer, and infectious diseases. In spite of this, OAS enzymes have been ignored as drug targets, and to date, there are no reports of compounds that can inhibit their activity. In this study, we have used homology modeling and virtual high-throughput screening to identify potential inhibitors of the human proteins OAS1, OAS2, and OAS3. Altogether, we have found 37 molecules that could exert a competitive inhibition in the ATP binding sites of OAS proteins, independently of the activation state of the enzyme. This latter characteristic, which might be crucial for a versatile inhibitor, was observed in compounds interacting with the residues Asp75, Asp77, Gln229, and Tyr230 in OAS1, and their equivalents in OAS2 and OAS3. Although there was little correlation between specific chemical fragments and their interactions, intermolecular contacts with OAS catalytic triad and other critical amino acids were mainly promoted by heterocycles with π electrons and hydrogen bond acceptors. In conclusion, this study provides a potential set of OAS inhibitors as well as valuable information for their design, development, and optimization.     

Amino acid-peptide-catalyzed enantioselective Morita-Baylis-Hillman reactions

Peptide-based catalysts in the presence of proline as co-catalyst have been found to catalyze the enantioselective ketone-based Morita-Baylis-Hillman reaction. The co-catalyst combination has afforded catalysis where enantioselectivities of up to 81% have been obtained.     

水稻根谷氨酰胺合成酶同工酶某些性质研究

对水稻根两种不同形式的谷氨酰胺合成酶（ＧＳｒａ和ＧＳｒｂ）进行了动力学性质研究．ＧＳｒａ对热比较稳定，而ＧＳｒｂ比较敏感；ＧＳｒａ的最适温度为５５℃，ＧＳｒｂ为４３℃．ＧＳｒａ和ＧＳｒｂ的最适ｐＨ都为７．５．ＧＳｒａ对Ｌ－谷氨酸、羟胺和ＡＴＰ的表观Ｋｍ分别为４．１６、０．６０和０．３４，而ＧＳｒｂ分别为１５．７３、０．６０和０．５８．ＭＳＯ对两者均表现为竞争性抑制作用