8-R-9苄基-9H-嘌呤衍生物的合成研究

采用 (Ph3 P) 2 PdCl2 为催化剂 ,DMF为溶剂 ,对 8 碘 9 苄基 9H 嘌呤与有机锡试剂RSnBu3 (R=乙烯基、2 噻吩基、2 呋喃基、苯乙炔基和苯基等 )之间的Stille偶合反应进行了研究 ,合成出了5种 8位取代的嘌呤衍生物。在反应温度为 80℃ ,n(8 碘 9 苄基 9H 嘌呤 )∶n (RSnBu3 )∶n〔(Ph3 P) 2 PdCl2 〕 =1 0∶1 2∶0 0 5的较佳工艺条件下 ,产品收率 4 1%～ 91%。用1H NMR、13 C NMR和MS对产物进行了表征     

Uric Acid: The Sperm-Release Pheromone of the Marine Polychaete Platynereis dumerilii

In the marine polychaete, Platynereis dumerilii, reproductive behavior in the two sexes is synchronized by the consecutive discharge of male and female sex-specific pheromones. After the female releases the eggs into the free water column, immediate fertilization is achieved by several males circling around the eggs emitting sperm clouds. We report the isolation and identification of the sperm-release pheromone present in the coelomic fluid of sexually mature females. Each step in isolation was guided by bioassay. Isolation methods included extraction and solvent partitioning and separation methods included ultrafiltration and high-performance liquid chromatography. Uric acid was identified as the sperm-release pheromone that is discharged by the female with release of the eggs. The threshold concentration for sperm release by males was determined as 0.6 M.     

8-碘-9-四氢吡喃-2-基-9H-嘌呤的合成

以 9-四氢吡喃 - 2 -基 - 9H-嘌呤、丁基锂和 I2 等为主要原料 ,四氢呋喃 ( THF)为溶剂 ,合成了 8-碘 - 9-四氢吡喃 - 2 -基 - 9H-嘌呤。考察了主要反应条件对反应的影响 ,确定了较佳工艺条件 :反应温度 - 78℃ ,n( 9-四氢吡喃 - 2 -基 - 9H-嘌呤 )∶ n(丁基锂 )∶ n(碘 ) =1 .0∶ 1 .5∶ 1 .5 ,反应时间 2 h。此条件下 ,产物收率 >90 %。同时 ,采用 1H- NMR、13C-NMR和 MS对产物结构进行了表征     

Milk feeding level and starter protein content: Effects on growth performance,blood metabolites,and urinary purine derivatives of Holstein dairy calves

The objective of this study was to investigate the effects of milk allowances equal to 526 g/d as moderate (MOD) versus 790 g/d of milk dry matter as high (HI), and starter diets containing 18% or 23% crude protein (CP), on growth performance, blood metabolites, and purine derivative (PD) excretion in the urine of dairy calves. A total of 52 female Holstein dairy calves (40.8 kg of body weight) were randomly assigned to the experimental diets. The treatments were (1) moderate milk and 18% CP starter diet (MOD-18CP); (2) MOD and 23% CP starter diet (MOD-23CP); (3) high milk and 18% CP starter diet (HI-18CP); and (4) HI and 23% CP starter diet (HI-23CP). Calves had free access to a starter feed and water and were weaned on d 53 but remained in the study until d 73. Urine samples were collected during the preweaning period (for 6 consecutive days between d 35 and 40) and postweaning period (for 6 consecutive days between d 65 and 70) to investigate urinary excretion of PD. Starter feed intake, β-hydroxybutyrate (BHB), and blood urea concentrations were reduced; however, average daily gain (ADG) and blood glucose levels increased in calves fed HI before weaning compared with MOD. During the preweaning period, high milk feeding increased total urinary PD excretion but decreased it after weaning. The 23CP diet resulted in higher feed intake and ADG before weaning and higher excretion of allantoin and total excretion of PD compared with the 18CP diet. The HI-23CP treatment resulted in the greatest withers and hip heights at weaning and final measurement, as well as the highest preweaning blood insulin concentrations. In terms of rumen development, MOD-23CP showed the greatest benefits based on starter intake, blood BHB concentration, and urinary excretion of PD. Based on the higher urinary excretion of PD found in HI-fed calves before weaning, it is possible that milk feeding overestimates estimated microbial yield. The results suggest that feeding starters with a higher proportion of CP may help maintain a more balanced ratio of CP to ME during high milk feeding, to avoid protein deficiency due to low starter intake. When calves are fed a high milk allowance, urine excretion of PD may be misinterpreted as a measure of estimated microbial growth and rumen development; this should be considered during calculations of estimated microbial yield in milk-fed calves.     

A Toxoplasma gondii Oxopurine Transporter Binds Nucleobases and Nucleosides Using Different Binding Modes

Toxoplasma gondii is unable to synthesize purines de novo, instead salvages them from its environment, inside the host cell, for which they need high affinity carriers. Here, we report the expression of a T. gondii Equilibrative Nucleoside Transporter, Tg244440, in a Trypanosoma brucei strain from which nucleobase transporters have been deleted. Tg244440 transported hypoxanthine and guanine with similar affinity (K_m ~1 µM), while inosine and guanosine displayed K_i values of 4.05 and 3.30 µM, respectively. Low affinity was observed for adenosine, adenine, and pyrimidines, classifying Tg244440 as a high affinity oxopurine transporter. Purine analogues were used to probe the substrate-transporter binding interactions, culminating in quantitative models showing different binding modes for oxopurine bases, oxopurine nucleosides, and adenosine. Hypoxanthine and guanine interacted through protonated N1 and N9, and through unprotonated N3 and N7 of the purine ring, whereas inosine and guanosine mostly employed the ribose hydroxy groups for binding, in addition to N1H of the nucleobase. Conversely, the ribose moiety of adenosine barely made any contribution to binding. Tg244440 is the first gene identified to encode a high affinity oxopurine transporter in T. gondii and, to the best of our knowledge, the first purine transporter to employ different binding modes for nucleosides and nucleobases.     

高效液相色谱法测定海水鱼中嘌呤含量

本文建立同时检测海水鱼中腺嘌呤、鸟嘌呤、次黄嘌呤、黄嘌呤的高效液相色谱检测方法。对部分海水鱼可食用部分及内脏中的4种嘌呤含量进行检测。结果表明,当使用Agilent ZORBAX Eclipse XDB-C18(4.6 mm×250 mm,5μm)色谱柱,以水-甲醇-冰乙酸-20%四丁基氢氧化铵(V/V/V/V=879/100/15/6)为流动相,设置流速为0.8 mL/min,柱温30℃,检测波长254 nm,进样量10μL时,4种嘌呤可完全分离且峰型较好。经方法学验证,得出此方法在0.1~400 mg/L范围线性关系良好,相关系数(R)在0.9998~1.0000之间,方法检出限范围0.0465~0.1056 mg/L。高效液相色谱检测方法精密度RSD在0.0200%~0.7000%之间,样品处理重复性腺嘌呤、鸟嘌呤、次黄嘌呤、黄嘌呤依次为1.2421%,0.9711%,0.8836%,1.9727%。加标回收率在94.2888%~102.9188%之间,适用于海水鱼中4种嘌呤的测定。经检测,不同种类海水鱼可食用部分(鱼眼睛、腹部鱼肉、背部鱼肉、鱼皮)嘌呤总含量由高到低依次为海鲈鱼、大菱鲆、金仓鱼、黄花鱼、美国红鱼、踏板鱼、鳕鱼。     

Uncoupling Protein 1 Does Not Produce Heat without Activation

Mitochondrial uncoupling protein 1 (UCP1) is the crucial mechanistic component of heat production in classical brown fat and the newly identified beige or brite fat. Thermogenesis inevitably comes at a high energetic cost and brown fat, ultimately, is an energy-wasting organ. A constrained strategy that minimizes brown fat activity unless obligate will have been favored during natural selection to safeguard metabolic thriftiness. Accordingly, UCP1 is constitutively inhibited and is inherently not leaky without activation. It follows that increasing brown adipocyte number or UCP1 abundance genetically or pharmacologically does not lead to an automatic increase in thermogenesis or subsequent metabolic consequences in the absence of a plausible route of concomitant activation. Despite its apparent obviousness, this tenet is frequently ignored. Consequently, incorrect conclusions are often drawn from increased BAT or brite/beige depot mass, e.g., predicting or causally linking beneficial metabolic effects. Here, we highlight the inherently inactive nature of UCP1, with a particular emphasis on the molecular brakes and releases of UCP1 activation under physiological conditions. These controls of UCP1 activity represent potential targets of therapeutic interventions to unlock constraints and efficiently harness the energy-expending potential of brown fat to prevent and treat obesity and associated metabolic disorders.     

嘌呤生物碱~（13）C－NMR化学位移的研究（Ⅰ）──化学位移加合和降阶模型

运用数学模型对天然嘌呤生物碱￣（１３）Ｃ－ＮＭＲ化学位移数据进行系统研究表明化学位移相对于未取代母体的增量具有良好的加合性和降解性，并对某些未知物的￣（１３）Ｃ－ＮＭＲ化学位移进行了预测。     

Comparative study of purine and pyrimidine nucleoside analogues acting on the thymidylate kinases of Mycobacterium tuberculosis and of humans

Thymidine monophosphate kinase (TMPK) from Mycobacterium tuberculosis (TMPKmt) is an attractive target for the design of specific inhibitors. This fact is the result of its key role in the thymidine pathway and of unique structural features in the active site observed by X-ray crystallography, especially in comparison to its human counterpart (TMPKh). Different 5-modified thymidine derivatives, as well as purine and pyrimidine analogues or C-nucleosides were tested on TMPKmt and TMPKh, and the results were rationalized by docking studies. 5-Halogenated 2'-deoxyuridines are the best inhibitors of TMPKmt found and present the highest selectivity indexes in favor of TMPKmt.