迷失的世界(17)

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人17β羟类固醇脱氢酶(17β-HSD)基因在家蚕系统中的表达(简报)

17β羟类固醇脱氢酶(17β-hydroxystero-id dehydrogenase,17β-HSD)能催化人体内类固醇性激素的形成和转化,例如它可以催化雌二醇与雌酮,雄烯二酮与睾酮之间的相互转化反应。人体内17β-HSD在胎盘组织含量最为丰富,催化17β-雌二醇等雌激素的生成,同时这些激素能够刺激乳腺瘤的增生。因此,如何抑制17β-HSD酶的过高活性,减少癌变发生的可能性,已成为目前这类癌症治疗的一个重要研究目标。目前,从胎盘组织中提取17β-HSD的方法,产量低,比活小,周期长,     

A review of mechanistic studies on aromatase (CYP19) and 17α-hydroxylase-17,20-lyase (CYP17)

In the conventional P-450 dependent hydroxylation reaction, the Fe(III) resting state of the enzyme, by a single electron transfer, is reduced to Fe(II), which reacts with O(2) to produce a Fe(III)-O-O intermediate. The latter following the transfer of another electron furnishes a ferric-peroxyanion, Fe(III)-O-O(-), which after protonation leads to the fission of the O-O bond resulting in the formation of Fe(V)O, the key player in the hydroxylation process. Certain members of the P-450 family, including CYP17 and CYP19, catalyze, at the same active site, not only the hydroxylation process but also an acyl-carbon bond cleavage reaction which has been interpreted to involve the nucleophilic attack of the ferric-peroxyanion, Fe(III)-O-O(-), on the acyl carbon to furnish a tetrahedral intermediate which fragments, leading to acyl-carbon cleavage. Evidence is presented to show that in the case of CYP17 the attack of Fe(III)-O-O(-) on the target carbon is promoted by cytochrome b(5), which acts as a conformational regulator of CYP17. It is this regulation of CYP17 that provides a safety mechanism which ensures that during corticoid biosynthesis, which involves 17α-hydroxylation by CYP17, androgen formation is avoided. Finally, a brief account is presented of the inhibitors, of the two enzymes, which have been designed on the basis of their mechanism of action. Article from the Special issue on 'Targeted Inhibitors'.     

keyword indes(1996,wol.17)

ＫＥＹＷＯＲＤＩＮＤＥＳ（１９９６，Ｖｏｌ．１７）Ａｂｕｎｄａｎｃｅ（３）：２３２ＡＣＡｓｅｒｕｍ（４）：４９９，５０７Ａｃｃｉｐｉｔｒｉｄａｅ（４）＝４８２Ａｄｅｎｏｈｙｐｏｐｈｙｓｉｓ（ｌ）：７８Ａｅｒｉａｌｒｅｓｐｉｒａｔｉｏｎ（２）：１５１Ａ...     

赤霉酸对枯草杆菌A_(17)生长的作用

我们曾经报导过,在以谷氨酸作为碳源的的合成培养基中加入赤霉酸,每毫升60微克,可以明显地刺激枯草杆菌_17的α—淀粉酶的形成。外源的3’,5’—环式—磷酸腺苷(5×10~(-3)M)和三磷酸腺苷(10~(-3)M)也有类似赤霉酸的作用、赤霉酸,3’,5’—环式     

Molecular modeling of the interaction of 17(20)Z- and 17(20)E-pregna-5,17(20)-dien-21-oyl amides with the nuclear receptor LXRβ

Eight isomeric 17(20)Z- and 17(20)E-pregna-5,17(20)-dien-21-oyl amides, conformationally rigid oxysterol analogues, differing in the structure of the amide moiety have been analyzed. Analysis of low energy conformers revealed that all 17(20)E-isomers had three main energy minima (corresponding to the values of the dihedral angle θ_20,21 (C17=C20-C21=O) about ～0°, ～120°, and ～240°); the most occupied minimum corresponded to θ_20,21 about ～0°. 17(20) Z-Isomers had either one or two pools of stable low energy conformations. Molecular docking of these compounds to the ligand-binding site of the nuclear receptor LXRβ (a potential target) demonstrated high probability of binding of E-isomers but not Z-isomers with this target. Results of the molecular modeling were confirmed by an experiment in which stimulation of triglyceride biosynthesis in Hep G2 cells in the presence of 17(20)E-3β-hydroxypregna-5,17(20)-dien-21-oyl (hydroxyethyl)amide was demonstrated.     

17种李属(广义)植物果实表皮微形态

应用蔡司荧光倒置显微镜观察17种(包含7栽培种)李属(广义)植物的果实表皮微形态特征。结果显示,果实表皮微形态多样,气孔复合体类型、气孔器形状、气孔大小、气孔密度及气孔周围纹饰等在李属(广义)植物不同类群中表现出各自独立的特点;一些性状如表皮细胞垂周壁式样、角质层纹饰和气孔复合体类型在属内各类群中出现分化规律,在各亚属之间表现出过渡性和连续性。研究表明,果实表皮微形态特征部分性状可作为李属(广义)植物识别的依据。果实表皮微形态特征在各类群之间变化,反映了不同类群对生态环境的适应。     

Design and synthesis of functionalized piperazin-1yl-(E)-stilbenes as inhibitors of 17α-hydroxylase-C17,20-lyase (Cyp17)

The synthesis of steroid hormones is critical to human physiology and improper regulation of either the synthesis of these key molecules or activation of the associated receptors can lead to disease states. This has led to intense interest in developing compounds capable of modulating the synthesis of steroid hormones. Compounds capable of inhibiting Cyp19 (Aromatase), a key enzyme in the synthesis of estrogens, have been successfully employed as breast cancer therapies, while inhibitors of Cyp17 (17α-hydroxylase-17,20-lyase), a key enzyme in the synthesis of glucocorticoids, mineralocorticoids and steroidal sex hormones, are a key component of prostate cancer therapy. Inhibition of CYP17 has also been suggested as a possible target for the treatment of Cushing Syndrome and Metabolic Syndrome. We have identified two novel series of stilbene based CYP17 inhibitors and demonstrated that exemplary compounds in these series have pharmacokinetic properties consistent with orally delivered drugs. These findings suggest that compounds in these classes may be useful for the treatment of diseases and conditions associated with improper regulation of glucocorticoids synthesis and glucocorticoids receptor activation.     

Syntheses of (14β,17α)-14-Hydroxy- and (14β,17α)-2,14-Dihydroxyestradiols and Their Activities

Structure 1 is proposed for the Inagami-Tamura endogenous digitalis-like factor (EDLF), and (14β,17α)-14-hydroxy- and (14β, 17α)-2,14-dihydroxyestradiols (2 and 3) were synthesized as models for studies on 1. The latter compound was remarkably potent in inducing a contractile response in isolated rat aorta and guinea pig left atrium.     

枯草杆菌A_(17)中含Poly(A)的RNA的分离和体外翻译

在以甘油(0.24％)或谷氨酸(0.5％)作为碳源,低磷(6.4×10~(-5)M)合成培养基,37℃下生长15小时的枯草杆菌A_(17),细胞中的含有poly(A)的RNA,可被oligo(dT)-纤维素分离。在培养基中加入赤霉酸(GA_3)30 μg/ml的情况下,含poly(A)的 RNA(峰Ⅱ)约为上柱总RNA的0.16～1.27％,不加GA_3的则为0.16～0.45％。这种含poly(A)的RNA能在麦胚非细胞合成系统中刺激~3H-亮氨酸掺入蛋白质,可为对照的4～8倍,其放射比活性为7000～23000 cpm/μg RNA,说明这种含 poly(A)的 RNA具有mRNA活性。     

Hydroxybenzothiazoles as new nonsteroidal inhibitors of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1)

17β-estradiol (E2), the most potent estrogen in humans, known to be involved in the development and progession of estrogen-dependent diseases (EDD) like breast cancer and endometriosis. 17β-HSD1, which catalyses the reduction of the weak estrogen estrone (E1) to E2, is often overexpressed in breast cancer and endometriotic tissues. An inhibition of 17β-HSD1 could selectively reduce the local E2-level thus allowing for a novel, targeted approach in the treatment of EDD. Continuing our search for new nonsteroidal 17β-HSD1 inhibitors, a novel pharmacophore model was derived from crystallographic data and used for the virtual screening of a small library of compounds. Subsequent experimental verification of the virtual hits led to the identification of the moderately active compound 5. Rigidification and further structure modifications resulted in the discovery of a novel class of 17β-HSD1 inhibitors bearing a benzothiazole-scaffold linked to a phenyl ring via keto- or amide-bridge. Their putative binding modes were investigated by correlating their biological data with features of the pharmacophore model. The most active keto-derivative 6 shows IC₅₀-values in the nanomolar range for the transformation of E1 to E2 by 17β-HSD1, reasonable selectivity against 17β-HSD2 but pronounced affinity to the estrogen receptors (ERs). On the other hand, the best amide-derivative 21 shows only medium 17β-HSD1 inhibitory activity at the target enzyme as well as fair selectivity against 17β-HSD2 and ERs. The compounds 6 and 21 can be regarded as first benzothiazole-type 17β-HSD1 inhibitors for the development of potential therapeutics.     

2006年第17届国际生物学奥林匹克竞赛(7)

理论试卷B 生态学(7题,12分) 为了解犰狳的食性,一个科研小组进行了一项植被调查,并比较犰狳粪便中的残留物. 43 科学家们在向日葵、玉米和天然草场中直线行进,他们每50 m取样1次,一个样方是1 m2,记录植被的种类、密度、覆盖情况和物候情况.以下哪种技术被用到了?     

2006年第17届国际生物学奥林匹克竞赛(4)

理论测试单元A 植物解剖学和植物生理学 下列哪组关键词说明木质部水分运输？ A．根毛，阳离子浓度，蒸腾作用 B．蒸腾作用，张力，吐水 C．蒸腾作用．水的内聚力．根压     

赤霉酸对枯草杆菌A_(17)的碱性磷酸酯酶的作用

赤霉酸(GA_3)能够刺激枯草杆菌A_(17)α-淀粉酶形成,这种作用可被天门冬酰胺阻抑。已有报导,GA_3也可以增强大麦种子糊粉层细胞内酸性磷酸酯酶的形成及向细胞的释放。但是,所释放的酶不含有碱性磷酸酯酶。革兰氏阳性细菌枯草杆菌产生许多胞外酶,这些胞外酶的结构基因,在一定的生长时期和生长条件下可以表达,合成这些酶蛋白质。枯草杆菌的胞外酶中只含有碱性磷酸酯酶而不含有酸性磷酸酯酶。本文初步报导外源GA_9对枯草杆菌A_(17)碱性磷酸酯酶的形成的刺激作用。     

2006年第17届国际生物学奥林匹克竞赛(5)

理论测试单元A 动物解剖与生理学 体温调节是生物生存的基础.产热与散热的平衡决定体温.在爬行类、两栖类和鱼类等脊椎动物中,体温在一定范围内波动.在鸟类与哺乳动物中存在反射机制使体温保持在1个较窄的范围内,不论环境温度如何波动.     

2006年第17届国际生物学奥林匹克竞赛(6)

理论试卷B 动物解剖与生理学(9个问题,16分) 22 图A,B表示激素相互作用的机理,在图A与B的空格中用给定的每一个代码填空以完成这些图.在答案纸上写下答案.     

HMG_(17)非组蛋白与转录活性基因的关系

 用核内蛋白质与经0.4mol/L NaCL抽提后的细胞核重组,以DNA酶I消化法为测定活性基因的指标,观察猪胸腺HMG_(17)非组蛋白对细胞核中活性基因的影响。结果显示:猪胸腺HMG_(17)使细胞核对DNA酶I作用的敏感性增加,因此认为HMG17为使细胞核胞核中基因呈较大活性的重要因素。     

[A_(15)Asn,A_(17)Pro,A_(21)Ala]-胰岛素的体内外生物活性

对胰岛素的研究使得许多生命科学中的重要问题被认识．然而对于胰岛素结构和功能关系,仍有许多不清楚的地方．在胰岛素Ａ链的Ｎ端和Ｃ端各有一个螺旋区：Ａ２－８和Ａ１２－１８．杨士珍［１］的研究表明：缺失Ａ１２－１８肽段的Ａ链类似物虽然能和天然Ｂ链重组,但其重组产物只保留了天然胰岛素的约６％的体内外生物活性．这说明Ａ１２－１８对胰岛素的生物活性十分重要．但是这一结果还不能说明是Ａ１２－１８螺旋还是Ａ１２－１８肽段对胰岛素的生物活性十分重要．根据Ｃｈｕｏ－Ｆａｓｍａｎ法,在含有Ａｓｎ和Ｐｒｏ的肽段中不能形成…