α-Glucosidases

This review highlights the main properties of mammalian, plant, and microbial alpha-glucosidases. Special attention is given to the classification of these enzymes, possible catalytic mechanisms, their tertiary structure, and the structure of major inhibitors. Experimental data on the elucidation of amino acid residues essential for catalysis are also discussed.     

α-catenin

Downregulation or loss of α-catenin occurs in multiple human cancer types. The traditional view of α-catenin is that it is one of the core components of the E-cadherin-catenin complex and is required for maintaining the integrity of the intercellular adherens junction, a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. Therefore, loss of α-catenin can result in loss of cell-cell adhesion, a common characteristic of cancer cells. There is an emerging recognition; however, that α-catenin also regulates multiple signaling pathways independent of adherens junctions. For instance, α-catenin functions as a tumor suppressor in E-cadherin-negative basal like breast cancer cells by inhibiting NF-κB signaling. In this perspective, we discuss the role and mechanisms of α-catenin in regulating several signaling pathways in cancer.     

Synthesis ofα-triazolylα-amino acid derivatives

Summary We report the synthesis of-triazolyl-amino esters by 1,3 dipolar cycloaddition of acetylenic compounds and-azido-amino esters.     

Synthesis of 7,8α-dihydro-14α-deoxyecdysteroids

A Pd-C-catalyzed hydrogenation in methanol and in the presence of sodium methylate is a simple, convenient and high yielding reduction method to convert the 7,14-dien-6-one ecdysteroids to their corresponding 7,8α-dihydro-14α-deoxyecdysteroids.     

α-LNA (α-D-Configured Locked Nucleic Acid)

Abstract

Two pyrimidine α-LNA nucleoside monomers have been synthesised and incorporated into α-configured oligonucleotides. A fully modified mixed α-LNA sequence displays unprecedented parallel stranded hybridisation with complementary RNA and a remarkable selectivity for RNA over DNA. Modelling shows α-LNA : RNA to form an extended duplex with a very broad major groove.     

转化生长因子α

转化生长因子α(transforming growth factor α,TGFα)是50个氨基酸的单链多肽,由160个氨基酸的前体加工而成。由于表皮生长因子(EGF)受体是 TGFα的功能性膜受体,因此,TGFα的许多生物学效应与 EGF 相似。TGFα最主要的功能是通过自分泌机制维持转化细胞的恶性生长。     

转化生长因子α

转化生长因子是一种主要是由肿瘤细胞产生的小肽分子,其前体为１６０个氨基酸,成熟体为５０个ａａ残基,各种表式的ＴＧＦａ均具有生物活性。ＴＧＦａ为分泌性蛋白,它与细胞表面的表皮生长因子受体结合,以自分泌和旁分泌的形式参与对细胞增殖和分化的调节,ＴＧＦａ与肿瘤密切相关,大多数肿瘤中已发现有ＴＧＦａ高表达,ＴＧＦａ具有肿瘤诊断、预后以及治疗临床外伤等多方面的应用价值。     

α-synuclein fate

The accumulation of α-synuclein is critical for the development of Parkinson disease (PD), and unraveling the mechanisms that regulate α-synuclein levels is key to understanding the pathophysiology of the disease. We recently found that USP9X deubiquitinates α-synuclein, and that this process determines the partition of α-synuclein between the proteasomal and autophagy pathways. By manipulating USP9X levels, we observed that monoubiquitinated α-synuclein is degraded by the proteasome, whereas deubiquitination of α-synuclein favors its degradation by autophagy. As USP9X levels and activity are decreased in α-synucleinopathy brains, USP9X may now represent a novel target for PD.     

α-环糊精葡萄糖基转移酶催化合成α-熊果苷

以对苯二酚和麦芽糊精为底物,通过α-环糊精葡萄糖基转移酶和淀粉葡萄糖苷酶的两步酶法反应体系催化合成α-熊果苷。优化后的催化条件:以葡萄糖当量(DE)值为8%~10%的麦芽糊精作为供体底物,麦芽糊精60g/L,对苯二酚150 mmol/L,缓冲液p H 6.0,在40℃下反应24 h。在此反应条件下,α-熊果苷的产量为3.17 g/L,对苯二酚转化率为7.77%。通过萃取法对α-熊果苷进行了初步分离,再经高效液相色谱-电喷雾串联质谱技术进行了结构测定,确定产物为α-熊果苷。     

微生物合成11α-羟基-16α,17α-环氧孕酮的动力学

对耐温黑根霉菌丝体催化16α,17-α-氧孕酮生成11α-羟基-16α,17α-环氧孕酮的反应体系进行了研究,考察了不同反应时间、不同菌体量和底物质量浓度对11α-羟化反应的影响,建立了相应的动力学模型,其方程为r=0.031Sr/1.05＋Sr。结果表明：提高菌体质量浓度有利于提高反应速率;底物浓度与反应初速率的关系与米氏方程相似。     

Metabolism of 17β-hydroxy-2α,3α-cyclopropano-5α-androstane in the rabbit

The neutral urinary excretion products of 17β-hydroxy-2α,3α-cyclopropano-5α-androstane from the rabbit, dosed orally, were investigated. Column chromatography yielded five crystalline metabolites which were identified by GLC and spectroscopic measurements. Three of these substances were hydroxylated in the 4α-position and one in the 6a-position with the cyclopropane ring intact. The fifth substance, 17β-hydroxy-3β-methyl-5α-androstan-2-one, can be derived from initial hydroxylation of the cyclopropane ring at C-2 followed by ring opening. The dosed substance and triol material was shown to be present by GLC and m.s. measurements. GLC determinations show that hydroxylation has occurred at C-4?C-6>C-2.     

IKKα的研究进展

IκB激酶(IKK复合体)是NF-κB信号转导途径成员之一,包括3个亚基:催化亚基IKKα、IKKβ和调节亚基IKKγ。无刺激时,NF-κB与抑制蛋白IκB家族的一个成员结合,或者与无活性前体(如p100)结合而以无活性形式存在。在外界信号如TNF-α或淋巴毒素β等刺激下,经过复杂的信号转导,IKK复合体被激活,导致IκB和(或)p100发生磷酸化,结果NF-κB被释放出来,进入细胞核内激活靶基因。最新研究发现在TNF-α刺激下,IKKα可直接进入细胞核内,通过催化组蛋白H3磷酸化进而激活特定NF-κB应答基因的表达。IKKα是首次发现的信号转导途径中直接进入细胞核内调节基因表达的上游成分,为NF-κB信号转导途径的研究开辟了新的道路。     

Nα-formyl-norleucyl-leucyl-phenylalanyl chloromethylketone

Summary N-formyl-norleucyl-leucyl-phenylalanine-chloromethyl ketone is chemotactic for, and induces lysosomal enzyme release from rabbit peritoneal neutrophils over essentially the same range of concentrations as does the free acid form of the same peptide (Na-formyl-norleucyl-leucyl-phenylalanine-OH). The chloromethyl ketone derivative does however differ from the free acid in respect to its ability to interact with the neutrophil and cause deactivation or desensitization to cytochalasin B. Neutrophils preincubated in the cold with the chloromethyl ketone followed by washing have cytochalasin B sensitivity conferred upon them, as measured by the release of lysosomal enzymes. The degree of release induced by this pre-treatment appears to be related to the initial responsiveness of the cells. This is in contrast to the free acid where no cytochalasin B sensitivity in conferred under any circumstances. Thus, the chloromethyl ketone, unlike the free acid, appears to irreversibly activate the cell. Desensitization to the late addition of cytochalasin B is also significantly retarded when the chloromethyl ketone derivative is compared to the free acid form of the peptide. These studies suggest that the chloromethyl ketone derivative of the peptide may covalently interact with the neutrophil receptor.     

胸腺素α原研究进展

胸腺素原（prothymosin alpha ProTα）是一种强酸性的蛋白,进化上高度保守,分布极其广泛。ProTα氨基酸序列的特征除前28个氨基酸与胸腺素α1完全相同外,ProTα有明显的中心酸性区和亲核序列。ProTα具有广泛的生物学活性,在细胞增殖、免疫调控和生殖活性等多方面起重要作用。     

雌激素受体α36

雌激素受体(estrogen receptor,ER)属核受体超家族成员之一,主要包括ER-α66、ER-α36、ER-α46和ER-β,它们通过与相应配体——雌激素的结合,在人体中发挥各种不同的功能。ER-α36是最近新发现的一种雌激素受体,它是ER-α66的独特变异体,主要分布于细胞膜和胞浆中,能抑制ER-α66和ER-β的反式激活功能,并参与雌激素的非基因组活性信号通路,介导了临床乳腺癌抗雌激素药物治疗抵抗。     

α-肾上腺素受体

近年来,α-肾上腺素受体的研究进展迅速。放射配体结合试验的应用和一系列对α_1受体或α_2受体有高度选择性的激动剂、阻断剂的发现,对此均有促进作用。血管平滑肌突触后膜上同时存在有α_1及α_2受体。深入研究外周及中枢口受体的定位、分型及功能,不仅具有重要生理学意义,而且对研制新药和探讨药物作用机理也有理论指导意义。