寄生原虫嘌呤磷酸核糖转移酶研究进展

寄生原虫是一类单细胞寄生性原虫,包括利什曼原虫（Leishmania spp.）、锥虫（Trypanosoma spp.）、疟原虫（Plasmodium spp.）、刚地弓形虫（Toxoplasma gondii）、隐孢子虫（Cryptosporidium spp.）和艾美耳球虫（Eimeria spp.）等,可引起严重危害人类与动物健康以及对养殖业造成巨大经济损失的原虫病。寄生虫入侵宿主后的发育和繁殖需要大量的嘌呤核苷酸,相应的嘌呤碱基在嘌呤磷酸核糖转移酶的催化下生成对 应的嘌呤核苷酸。嘌呤磷酸核糖转移酶是一类参与嘌呤核苷酸补救合成的重要代谢酶,广泛存在于寄生原虫中。寄生原虫的嘌呤磷酸核糖转移酶主要包括腺嘌呤磷酸核糖转移酶和次黄嘌呤 - 鸟嘌呤 - 黄嘌呤磷酸核糖转移酶,两者在寄生原虫中分别催化腺嘌呤核苷酸、次黄嘌呤核苷酸、鸟嘌呤核苷酸和黄嘌呤核苷酸合成,从而参与寄生原虫的多个生化代谢过程,不仅为寄生原虫核酸生物合成等提供前体物质,还为虫体提供通用能量载体。由于寄生原虫的嘌呤补救途径明显区别于宿主的从头合成途径,且嘌呤磷酸核糖转移酶是寄生原虫嘌呤补救途径的关键酶,因而近年来寄生原虫嘌呤磷酸核糖转移酶成为抗原虫药物候选靶标的研究热点,以寄生原虫嘌呤磷酸核糖转移酶为潜在靶标,特异性筛选、设计抑制剂,并开发抗寄生原虫药物取得重要进展。以利什曼原虫、锥虫、疟原虫和弓形虫的嘌呤磷酸核糖转移酶为重点,综述寄生原虫嘌呤磷酸核糖转移酶的基本特征、生物学功能、抑制剂筛选与应用的研究进展,以期为抗寄生原虫药物靶标研究与新型抑制剂筛选提供参考。     

The serine protease inhibitors and SERPINE1/2 disrupt prostaglandin E2 production and hyaluronic acid retention in FSH‐stimulated pig cumulus–oocyte complexes

The serine proteases, tissue‐ and urokinase‐type plasminogen activators (PLAT and PLAU) and their inhibitors SERPINE1/2 are regulators of plasminogen to plasmin conversion. They are widely expressed in ovarian tissues, including granulosa and cumulus cells, and their expression is regulated by gonadotropins. The aim of this work was to assess the effect of serine protease inhibitors (aprotinin and AEBSF) and SERPINE1/2 on FSH‐induced cumulus cell expansion, the production of prostaglandin E2 (PGE2) and retention of hyaluronic acid (HA) in expanding cumulus. The serine protease activity proved to be essential for the production of PGE2 and also for the retention of HA; the inhibition of plasminogen activators by SERPINE1/2 had the same effect. Collectively, these data indicate that plasmin is required for proper function of expanding cumulus cells in vitro and presumably also in vivo in the pre‐ovulatory follicles.     

大麦根中多胺含量和转化与耐盐性的关系

用0、50、100、200和300mmol·L-1NaCl对2个耐盐性不同的大麦品种鉴4(J4,耐盐性较强)和科品7号(KP7,耐盐性较弱)幼苗处理8d后,其干重均随着NaCl浓度增加而显著下降,叶片MDA含量和相对电导率相应增加。与对照相比,J4干重的降低要小于KP7,MDA含量和相对电导率也比KP7低。在盐胁迫下,大麦幼苗根系的多胺含量和种类也有显著的变化,随NaCl浓度的增加,腐胺(Put)含量先下降后上升,而亚精胺(Spd)含量的变化则相反,这种多胺含量变化的盐浓度阈值J4大于KP7。多胺合成抑制剂D-Arg、二氟甲基鸟氨酸(DFMO)和甲基乙二醛双(鸟嘌呤腙)(MGBG)可以显著降低盐胁迫下多胺含量,不同程度上加重了盐胁迫的伤害,表明植物体内多胺在盐胁迫适应中具有重要的作用。     

Mechanisms of resistance to acetyl-coenzyme A carboxylase inhibitors: a review

Resistance to acetyl-coenzyme A carboxylase (ACCase) inhibitors has developed in at least 10 grass weed species in recent years. In most instances, resistance is conferred by an ACCase alteration in the resistant biotypes that reduces sensitivity to aryloxyphenoxypropionate (AOPP) and cyclohexanedione (CHD) herbicides. Analysis of ACCase from many of these resistant weed biotypes suggests the presence of different mutations, each conferring a different pattern and level of resistance to various AOPP and CHD herbicides. In all cases analyzed to date, resistance is controlled by a single dominant or semi-dominant nuclear gene. In several weed biotypes, resistance is conferred by enhanced herbicide detoxification, primarily through elevated expression or activity of cytochrome P450 monooxygenase(s). This mechanism can confer cross-resistance to herbicides from other chemical classes with different modes of action. Finally, multiple herbicide resistance, i.e. the acquisition of several different resistance mechanisms, has been reported in some weed biotypes. ©1997 SCI     

金潮原因种铜藻外源无机碳利用特征初步研究

为揭示铜藻(Sargassum horneri)对无机碳利用的基本特性及铜藻在漂浮过程中生物量迅速累积并最终发展为金潮的生理生态学机理,以我国近海金潮原因种铜藻为研究对象,在不同pH (6.5、8.0和9.5)条件下研究了添加TRIS缓冲剂、碳酸酐酶抑制剂(AZ、EZ)和阴离子交换蛋白抑制剂(DIDS)后藻体的固碳速率、光合作用-无机碳响应曲线(P-C曲线)及pH漂移曲线。结果显示,TRIS缓冲剂对铜藻的固碳速率无显著影响(P>0.05),而3种抑制剂均显著(P<0. 05)抑制铜藻的固碳速率且抑制效率从大至小依次为DIDS> EZ>AZ。藻体的固碳速率随着外源无机碳浓度的增加而增加,并渐趋饱和。此外,藻体的最大固碳速率(V_max)随着pH的升高而降低,而半饱和常数(K_0.5)则随着pH的升高而升高,藻体的pH补偿点为9.0左右。结果表明,铜藻既可以利用海水中的CO_2也可以利用HCO_3^-进行光合作用;并且铜藻对HCO_3^-的吸收存在通过阴离子交换蛋白直接转运吸收和利用碳酸酐酶将HCO_3^-转化为CO_2后再吸收两种方式。对HCO_3^-的高效吸收利用能力可能是铜藻保证维持较高光合作用、快速积累生物量并最终演变为金潮的重要因素之一。     

A comparative molecular field analysis study of obtusifoliol 14α-methyl demethylase inhibitors

This report describes the development of a Comparative Molecular Field Analysis (CoMFA) model from a set of obtusifoliol 14α-methyl demethylase (DM) inhibitors to aid in the design of herbicides targeting sterol biosynthesis. CoMFA is a three-dimensional (3-D) quantitative structure–activity relationship (QSAR) method that is useful in the probing of receptor binding sites when experimental structure data are unavailable. Conformational analysis and SAR of some rigid and active analogs were used to build the initial model using the active analog hypothesis. The model was subsequently used to design compounds that retain the active site shape requirements, but incorporate physical properties that favor soil-applied herbicidal action. In addition, a second-generation CoMFA model incorporating the newly designed inhibitors was developed and represents the current understanding of the DM binding site. This model was derived from a pharmacophore developed from two methods, the active analog approach as well as from the Catalyst program. The fact that two independent methods produced a similar pharmacophore strengthens the validity of the model. © 1999 Society of Chemical Industry     

苯甲酰胺类磷酸二酯酶-4抑制剂的设计与合成

目的 合成6个苯甲酰胺类磷酸二酯酶-4抑制剂。方法 以异香兰素为原料,经过成醚反应、氧化反应、Schotten-Baumann反应等制备目标化合物。结果 成功制备了6个目标化合物：Benzoic acid,4-[[3-（isobutoxy）-4-methoxybenzoyl]amino]（T1）,Benzamide,4-[[3-（isobutoxy）-4-methoxybenzoyl]amino]（T2）,Benzamide,4-（isobutoxy）-3-methoxy-N-[4-[[（1-methylethyl）amino]sulfonyl]phenyl]（T3）,Benzoicacid,4-[[3-（cyclopentyloxy）-4-methoxybenzoyl]amino]（T4）,Benzamide,4-[[3-（cyclopentyloxy）-4-methoxybenzoyl]amino]（T5）,Benzamide,4-（cyclopentyloxy）-3-methoxy-N-[4-[[（1-methylethyl）amino]sulfonyl]phenyl]（T6）,收率分别为66.7%、65.7%、18.4%、46.7%、76.8%和12.4%,其中化合物T1、T2、T3、T5、T6为新化合物。结论 所得产物的化学结构经¹H-NMR、MS谱确证,与目标化合物相符。     

杧果乙烯抑制剂的筛选及其采后保鲜效果研究

比较研究不同浓度乙烯抑制剂AOA(aminooxyacetic acid)、AIB(α-amino-isobutyric acid)、AVG (Aminoethoxyvinyl glycine hydrochloride)、ATA(3-amino-1,2,4-triazole)、1-MCP(1-methylcyclopropene)、精胺、亚精胺对采后杧果(Mangifera indica L．)乙烯释放的抑制效果,以期筛出最佳乙烯抑制剂并探究其对杧果的贮藏保鲜效果。结果表明：不同浓度乙烯抑制剂处理杧果,均可降低杧果果实乙烯释放量,其中1 mmol/L精胺、10 mmol/L亚精胺和50 mmol/L ATA可有效延缓硬度、可滴定酸(Titratable acid, TA)下降,维持较高VC(Vitamin C)和TSS(Total soluble solids)含量。综合分析,精胺、亚精胺、ATA处理可有效延缓采后杧果果实软化,为采后杧果贮藏保鲜提供技术支持。     

四种SBIs类杀菌剂对不同发育阶段小麦赤霉病菌的毒力及其作用方式

为明确不同发育阶段小麦赤霉病菌对甾醇生物合成抑制剂类(SBIs)杀菌剂的敏感性差异及杀菌剂的作用方式,对4种SBIs类杀菌剂进行了室内毒力测定及田间药效试验。室内毒力测定结果表明:不同发育阶段小麦赤霉病菌对4种SBIs类药剂的敏感性存在较大差异,其敏感性由高到低依次为菌丝生长阶段和产孢阶段芽管伸长阶段孢子萌发阶段;其中,戊唑醇对菌丝生长、产孢、芽管伸长和孢子萌发阶段的EC50值分别为0.686、0.191、3.532和3.825μg/m L,咪鲜胺分别为0.063、0.305、0.827和36.581μg/m L,苯醚甲环唑分别为0.873、3.659、5.687和79.465μg/m L,烯唑醇分别为1.961、33.658、41.881和54.986μg/m L。显微观察4种SBIs类杀菌剂对小麦赤霉病菌菌丝生长和孢子萌发形态的影响,发现杀菌剂处理后菌丝末端分枝增多,新生菌丝伸长受阻,菌丝体局部膨大,有时可见菌丝及芽管的消解。田间试验结果表明:用量为有效成分100 g/hm2的戊唑醇、200 g/hm2的咪鲜胺和200 g/hm2的苯醚甲环唑对小麦赤霉病的保护效果为77.15%~79.26%,治疗效果为70.64%~72.77%,于发病前后使用均可有效防治该病害。