Antitumor agents-CLXXV. Anti-tubulin action of (+)-thiocolchicine prepared by partial synthesis

(+)-Thiocolchicine (2b) was prepared from (±)-colchicine (1) in a five-step reaction sequence that included chromatographic separation of appropriate camphanylated diastereomers. Acid hydrolysis of the (+)-diastereomer, followed by acetylation, yielded the desired product 2b. (+)-Thiocolchicine has 15-fold lower inhibitory activity against tubulin polymerization than (−)-thiocolchicine, and is 29-fold less potent for inhibiting growth of human Burkitt lymphoma cells. The enantiomer 2a, prepared from the (−)-camphanylated diastereomer, had potent activity in all assays comparable to that of (−)-thiocolchicine prepared by other methods. These results support the hypothesis that the proper configuration of colchicine-related compounds is an important requirement for their anti-tubulin action.     

枯草杆菌蛋白酶E的156和165位突变

应用定点突变方法,在M222A突变的枯草杆菌蛋白酶E基因上进行E156S和V165I定点突变. 将突变基因插入大肠杆菌-枯草杆菌穿梭质粒pBE-2中,在碱性和中性蛋白酶缺陷型的枯草杆菌DB104中进行表达,得到突变种(M222A,E156S)和(M222A,E156S,V165I)蛋白酶E. 性质测定表明,E156S突变使蛋白酶比活力增加90%,并不影响酶的热稳定性和抗氧化性. 而V165I突变使蛋白酶比活力降低.     

FK-506结合蛋白对钙释放通道的调控

细胞内自由钙作为一种重要的细胞信使广泛地参与细胞生理功能调控.胞内钙库(内质网系和肌浆网系)对调节细胞内自由钙水平起着重要的作用.钙库膜上的钙释放通道(ryanodine受体和三磷酸肌醇受体)受许多因素调控,其中之一就是新近研究得相当多的FK506结合蛋白.免疫抑制剂FK506能特异地结合钙库上一种分子质量为12 ku左右的蛋白,这种FK506结合蛋白与钙释放通道形成一种紧密连接的复合体,在正常生理情况下对钙释放通道起着十分重要的调控作用.     

转铁蛋白分型及其基因频率分布

用固相pH梯度(pH 5.05～5.60)等电聚焦技术对随机抽取的188名北京地区健康汉族人的血清转铁蛋白(Tf)进行分型调查,并统计基因频率,检出了在中国还未见报道的Tf^C3基因.其表型分别是：TfC1, TfC2, TfC1C2, TfC1C3, TfC1Dchi, TfC2Dchi.Tf^C1=0.7420, Tf^C2=0.2420, Tf^C3=0.0027, Tf^Dchi=0.0133, 符合Hardy-Weinberg定律, 并与其他已见报道的汉族 Tf基因频率大致相符.     

Sequence variation and genetic diversity in the giant panda

About 336–444 bp mitochondrial D-loop region and tRNA gene were sequenced for 40 individuals of the giant panda which were collected from Mabian, Meigu, Yuexi, Baoxing, Pingwu, Qingchuan, Nanping and Baishuijiang, respectively. 9 haplotypes were found in 21 founders. The results showed that the giant panda has low genetic variations, and that there is no notable genetic isolation among geographical populations. The ancestor of the living giant panda population perhaps appeared in the late Pleistocene, and unfortunately, might have suffered bottleneck attacks. Afterwards, its genetic diversity seemed to recover to some extent. Project supported by the “8.5” Key Project of Chinese Academy of Sciences, the Chairman Foundation of Chinese Academy of Sciences, K. C. Wang Education Foundation, the Applied Basic Research Foundation of Yunnan, the National Natural Science Foundation of China, the Special Foundation for Returned Chinese Scientists, and Zoological Society of San Diego.     

球形红杆菌积累聚β-羟基链烷酸(PHA)的研究

通过对球形红杆菌(Rhodobacter sphaeroides)生长和积累聚卢-羟基链烷酸(PHA)条件的研究,确定采用两段培养法提高PHA的产量。第一阶段提供适合菌体生长的条件:以葡萄糖作碳源,尿素为氮源,光照微好氧培养。第二阶段则提供使菌体积累PHA的条件:补加乙酸钠厌氧光照培养。经两段培养后菌体PHA含量可占细胞干重的45％,PHA产量每升发酵液可达1.7g。     

不同光学异构体组成的氯氰菊酯对敏感及抗性家蝇的神经电生理学研究

采用敏感家蝇(Musca domestica vicina L.)及由5种不同光学异构体组成的氯氰菊酯选育的抗性家蝇中胸足离体标本,观测五种药剂对足感觉神经纤维冲动发放的影响。各种异构体组成的氯氰菊酯均可引起感觉神经纤维发放的增加,然后逐渐降低,直至完全阻断。以阻断时间和加药剂量为参数,求出神经敏感度。结果表明：五种药剂作用于敏感家蝇的神经敏感度与室内生物测定的LD₅₀值(μg/头)无相关性,而与供试药剂中反α体与顺α体的比例有关,反α体所占比例越多的药物,神经敏感度越高。抗性家蝇的神经敏感度与敏感 家蝇相比大幅度下降,可以认为神经敏感度降低是家蝇对氯氰菊酯产生抗性的主要机制。抗性家蝇中,氯氰菊酯品系(RC₁)的抗生水平最高,但它的神经敏感度较其它抗性品系也高,由此推测,RC₁,的抗性机制与其它晶系有所不同。     

高必需氨基酸转基因马铃薯的研究

８０年代以来,马铃薯遗传转化系统日趋成熟,转基因工程植株已被广泛应用于基础科学研究［１］。作为食物蛋白和能量主要来源的马铃薯,提高其蛋白质含量及质量的遗传工程研究正受到人们的普遍关注［２］。Ｙａｎｇ等［２］将旨在改善氨基酸平衡的ＣＡＴ－ＨＥＡＡＥ（氯酶素乙酰转移酶－高含量人体必需氨基酸）融合基因导入马铃薯,获得了Ｓｏｕｔｈｅｒｎｂｌｏｔ、Ｎｏｒｔｈｅｒｎｂｌｏｔ、Ｗｅｓｔｅｒｎｂｌｏｔ的证据,但尚缺少氨基酸分析的资料。玉米醇溶蛋白（ｚｅｉｎ）［３］是一个富含甲硫氨酸的贮存蛋白,它和人工合成的ＨＥ…     

干旱和湿润生境下辽东栎群体遗传结构及其适应意义的初步研究

应用同工酶分析方法,测定北京市东灵山区两个分别代表干旱和湿润生境的辽东栋（ＱｕｅｒｃｕｓｌｉａｏｔｕｎｇｅｎｓｉｓＫｏｉｚ．）群体的遗传结构。共分析统计了１３ 个酶系统３０ 个位点。结果表明：辽东栎群体内部存在丰富的遗传变异（多态位点百分率为８６．６％ ,等位基因平均数为２．２５）。两群体遗传结构的相似性程度很高（Ｄ＝ ０．０２９, ＧＳＴ＝ ０．０４８）;但在个别位点上仍存在较大差异,这些差异的产生可能与对小生境的适应有关。对不同年龄段的初步分析结果显示,基因频率的动态变化可能有其适应意义