INTERACTION OF DISTAMYCIN A AND NETROPSIN WITH QUADRUPLEX AND DUPLEX STRUCTURES: A COMPARATIVE 1H-NMR STUDY

ABSTRACT

Homonuclear NMR techniques have been used to investigate the interactions of the minor groove binding agents distamycin A (Dist-A) and the related drug netropsin (Net) with three quadruplexes characterized by different groove widths: [d(TGGGGT)]₄ (Q1), [d(GGGGTTTTGGGG)]₂ (Q2), and d(GGGGTTGGGGTGTGGGGTTGGGG) (Q3). Netropsin has been found to be in a fast chemical exchange with all three kinds of quadruplexes, whereas Dist-A interacts tightly with Q1 and, at a less extent, with Q2. In order to determine the degree of selectivity of Dist-A for two- rather than four-stranded DNA, we titrated with Dist-A an equimolar solution of Q1 and the duplex d(CGCAAATTTGCG)₂ (D). This comparative ¹H-NMR study allowed us to conclude that Dist-A and, consequently, Net possess higher affinity for duplex DNA.     

PROPYNYL GROUPS IN DUPLEX,HAIRPIN AND TRIPLEX DNA: 7-DEAZAPURINES AND 9-DEAZAPURINES

Oligonucleotides containing 7-deazapurines or 9-deazapurines with propynyl groups at the 7- or 9-position were prepared. The stabilizing effect of the propynyl group was studied on DNA duplexes, hairpins and triplexes.     

SYNTHESIS AND BIOLOGICAL ACTIVITY OF 5-SUBSTITUTED ANTI-CONSTRAINED ACYCLIC ANALOGS OF CYTIDINE AND URIDINE

Abstract

Abstract. A number of 5-substituted constrained acyclic analogs of cytidine and uridine have been prepared in which the glycosyl torsion angle is constrained in the anti conformation. Compounds 2a-c, 3a-c, 4, 5 and 6 were tested for activity against HCMV and HSV-1. Compounds 2a and 2b showed moderate activity against HCMV. Compound 2c exhibited a weak inhibitory activity against HSV-1. Compounds 2a, 3a, 4, 5, 6, 8, and 9 were screened for their anti-HIV or antitumor activity. None of them were active against HIV. However, compound 9 showed a 50% inhibition on MDA-MB-231/ATTC breast cancer cell growth at a concentration of 0.15 μM.     

6-SUBSTITUTED 5-FLUOROURACIL DERIVATIVES AS TRANSITION STATE ANALOGUE INHIBITORS OF THYMIDINE PHOSPHORYLASE

A combination of mechanism-based and structure-based design strategies led to the synthesis of a series of 5- and 6-substituted uracil derivatives as potential inhibitors of thymidine phosphorlase/platelet derived endothelial cell growth factor (TP/PD-ECGF). Among those tested, 6-imidazolylmethyl-5-fluorouracil was found to be the most potent inhibitor with a K_i-value of 51 nM, representing a new class of 5-fluoropyrimidines with a novel mechanism of action.     

滇黄芩甙A和B的结构

从龙胆科滇黄芩属植物滇黄芩(Veratrilla baillonii Franch)中分离得到两个新的酮二糖甙,经~1H NMR,~(13)C NMR,FAB-MS,MS,2D NMR,UV,IR等物理方法和化学反应,推定为:2,3,4,7-四甲氧基酮-1-O-β-D-葡萄糖(6←1)-β-D-木糖甙(1)和7-羟基-2,3,4-三甲氧基酮-1-O-β-D-葡萄糖(6←1)-β-D-木糖甙(2),分别命名为:滇黄芩甙A和滇黄芩甙B。     

BMP-2、-3、-6和-12在骨肉瘤细胞株中的表达

目的研究骨形态发生蛋白(bone morphogenetic protein,BMP)-2、-3、-6和-12在骨肉瘤细胞株中的表达,为下一步研究BMPs在骨肉瘤发生发展中的作用奠定基础。方法利用免疫细胞化学法和Western blot法检测BMP-2、-3、-6和-12在人骨肉瘤细胞株MG63、U2OS和大鼠骨肉瘤细胞株UMR106中的内源性表达。结果在MG63、U2OS和UMR106细胞中,BMP-2、-3和-6均呈不同程度的阳性表达;而BMP-12在这3株骨肉瘤细胞中则均为阴性,并且两种检测方法所得结果完全一致。结论BMP-2、-3和-6在人骨肉瘤细胞株MG63、U2OS和大鼠骨肉瘤细胞株UMR106中均有内源性表达;而这3株骨肉瘤细胞中均未检出BMP-12的表达。     

细锥香茶菜甲素和乙素的化学结构

从细锥香茶菜中分得两个新的二萜类化合物,命名为细锥香茶菜甲素和乙素(coetsinA&B)根据其光谱和化学数据,推定其化学结构为[1]和[2]。     

SYNTHESIS OF 8-AMINO AND 8-SUBSTITUTED AMINO DERIVATIVES OF ACYCLIC PURINE NUCLEOSIDE AND NUCLEOTIDE ANALOGS. ALKYLATION OF 8-SUBSTITUTED PURINE BASES

Two synthetic approaches were used for preparation of 8-amino-, 8-methyl- amino-, and 8-dimethylaminoadenine and -guanine analogs of PME and HPMP series: (a) direct modification of 8-bromopurine acyclic nucleotide analogs at the 8-position of the base, (b) alkylation of 8-modified purine bases with alkylation agents.     

SYNTHESIS AND IN VITRO CYTOTOXIC AND ANTIVIRAL ACTIVITIES OF 1-(2,5,6-TRIDEOXY-6-HALOGENOHEPT-5-ENOFURANURONONITRILE)THYMINE AND DERIVATIVES

ABSTRACT

All 1-(2,5,6-trideoxy-6-halogenohept-5-enofuranurononitrile)thymine and their 3′-O-TBDMS derivatives have been prepared and their configuration established. Some of these compounds are endowed with a cytotoxic or cytostatic activity in cell culture. The single most important factor affecting the cytotoxicity of these compounds is the presence on the molecule of a soft (electrofugal) halogen atom.     

应用量子化学方法研究茶多酚类抗氧化剂的构效关系

采用分子力学和量子化学从头计算方法,研究了不同结构茶多酚（Green tea polyphenol,GTP)抗氧化活性的构效关系。计算结果表明,茶多酚类的抗氧化活性与其释放活泼氢生成苯氧自由基的能力有关,添生大小与O－H间的Mulliken集居数、前线轨道能量、反应终态能量下降量及苯氧自由基稳定性有关。     

ELECTROPHORETIC STUDY OF 5-HYDROXYTRYPTOPHAN DECARBOXYLASE FROM BRAIN AND LIVER IN SEVERAL SPECIES

—An electrophoretic investigation in acrylamide gels of 5-hydroxytryptophan decarboxylase, obtained mostly from mouse, rat, and beef brain and also from beef and human liver, showed electrophoretic differences between species. With the exception of the rat, only one molecular species was found (the same in beef brain and liver). In the rat, polymers form spontaneously and are, at least in part, disaggregated by urea and by triton. Mouse-rat or beef-rat molecular hybrids form in the admixtures. No electrophoretic differences were found in five mice strains that were investigated. Techniques of electrophoretic analysis and of assay of 5-hydroxytryptophan decarboxylase are described, which can be easily applied to other enzymes, provided a substrate is available in radioactive form.     

AKT和PTEN在骨肉瘤中表达的相关研究

目的探讨骨肉瘤中AKT和PTEN表达的意义及其临床价值。方法采用免疫组织化学SABC法检测48例骨肉瘤、15例骨软骨瘤标本中AKT、PTEN表达的阳性细胞。结果AKT的阳性表达率在骨肉瘤中为87.5%,在骨软骨瘤中为33.3%,两者比较有显著差异(P<0.05);PTEN的阳性表达率在骨肉瘤中为41.7%,在骨软骨瘤中为86.7%,两者差异显著(P<0.01);在骨肉瘤中,AKT与PTEN呈负相关(r=-0.453,P<0.05)。AKT蛋白表达在有肿瘤复发、肺转移的骨肉瘤中的表达高于无复发及无肺转移的骨肉瘤(P<0.05),而PTEN则相反(P<0.05)。两者的表达均与年龄、性别、肿瘤的大小无关(P>0.05)。结论AKT蛋白的表达在骨肉瘤发生发展中起重要作用,PTEN则可抑制这一作用过程。     

3-6岁幼儿的Heath-Carter体型法研究

本文主要运用Heath-Carter体型测量法,对芜湖市区汉族441例(男222人,女219人)3-6岁的健康幼儿进行了体型分析.结果显示汉族幼儿随着年龄的增长,中因子值和内因子值略有下降,但变化不大,外因子值逐步上升,变化较快;男女孩各年龄组体型均值都是中因子值＞内因子值＞外因子值.幼儿期低龄段体型分布较集中,在随后的增长过程中,体型分布逐渐扩散,3-5岁男女各组体型均为偏内胚型的中胚型为主,6岁时男孩均衡中胚,女孩三胚层中间型比例增多.与布拉格幼儿相比,体型特征存在着显著性差异.     

视觉系统皮层下细胞的方位和方向敏感性

视觉方位、方向选择性曾被认为是高等哺乳动物视皮层细胞的特有功能。近年来大量的实验结果表明,视皮层下的外膝体神经元和视网膜神经节细胞都具一定程度的方位和方向敏感性,这些性质是遗传决定的,不受后天环境的影响。在外膝体内,已为视皮层细胞高度的方位、方向选择性和功能柱的形成做出了初步的分类与编组,提供了前级安排。这种皮层下的方位、方向敏感性细胞在发育过程中传递和加工了环境视觉信息,促进了视皮层更强的方位、方向选择性机制和方位功能柱的形成。外膝体在视觉信息平行处理通道的形成上起着分类集聚的重要作用。