Syntheses of cyclic prodrugs of RGD peptidomimetics with various macrocyclic ring sizes: evaluation of physicochemical, transport and antithrombic properties.

The objective of this work was to synthesize cyclic prodrugs 1a-d of RGD peptidomimetics 2a-d with various ring sizes (n[CH2] = 1, 3, 5 and 7) and to evaluate the effect of ring size on their transport, physicochemical, enzymatic stability, and antithrombic properties. The syntheses of cyclic prodrugs 1a-d were achieved by converging two key intermediates, Boc-Phe-O-CH2-OCO-OpNP (5) and H2N-(CH2)n-CO-Asp(OBzl)-OTce (8a-d), to give linear precursors Boc-Phe-O-CH2-OCO-HN-(CH2)n-CO-Asp(OBzl)-OTce (9a-d). The N- and C-terminus protecting groups were removed from 9a-d to give 10a-d. Linear precursors 10a-d were cyclized, and the remaining Bzl-protecting group was removed to produce cyclic prodrugs 1a-d in around 20% overall yield. The linear RGD peptidomimetics (2a-d) were synthesized using standard Boc-amino acid chemistry by solution-phase method. Increasing the ring size by adding methylene groups also increases the hydrophobicity of the cyclic prodrugs and parent RGD peptidomimetics. The transport properties of cyclic prodrugs 1c and 1d were 2.6- and 4.4-fold better than those of parent compounds 2c and 2d, respectively. These results suggest that increasing the hydrophobicity of the cyclic prodrugs and parent RGD peptidomimetics enhanced their transport properties. The hydrodynamic radii of the cyclic prodrugs were also smaller than those of their respective parent compounds, suggesting that the change in size may contribute to their transport properties. The chemical stability of the cyclic prodrugs was affected by the ring size, and the cyclic prodrug with the larger ring size (i.e. 1d) was more stable than the smaller one (i.e. 1a). All the cyclic prodrugs were more stable at pH 4 than at pH 7 and 10. Prodrug-to-drug conversion could be induced by isolated esterase as well as esterase found in human plasma. An increase in the length of methylene group (n[CH2] = 1, 3, 5, 7) enhanced the antithrombic activity of the prodrugs and the parent compounds. In summary, the ring size of cyclic prodrugs affected their transport, physicochemical, and antithrombic properties.     

培养大鼠颈上神经节单烟碱受体通道及突触电流的膜片钳研究

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脏器微血管对荧光素钠通透性的实验方法

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大鼠皂素蜕膜心肌肌钙蛋白Ca^2＋敏感性的实验研究

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硒对培养人胚肝细胞Ⅲ型前胶原,羟脯氨酸合成的影响

原代培养人胚肝细胞经１．１５６×１０￣(－７）ｍｏｌ／Ｌ硒预处理４ｈ,加入２０ｍｍｏｌ／Ｌ四氟化碳作用２０ｈ,观察硒对其Ⅲ型前胶原（ＰＣⅢ）和羟脯氨酸（Ｈｙｐ）生成的影响。结果培养液中ＰＣⅢ水平、细胞内Ｈｙｐ含量及细胞内外丙二醛（ＭＤＡ）水平均降低,与未加硒对照组比较差别有显著性（Ｐ＜０．０１）。而硒谷腕甘肽过氧化物酶（Ｓｅ－ＧＳＨ－ＰＸ）活性则较对照组显著增高（Ｐ＜０．００１）,且ＰＣⅢ水平与Ｓｅ－ＧＳＨ－Ｐ＿Ｘ／ＭＤＡ比值呈负相关（ｒ＝－０．９１５６,Ｐ＜０．０１）。提示硒可提高Ｓｅ－ＧＳＨ－Ｐ＿Ｘ／ＭＤＡ比值,抑制脂质过氧化激发的肝细胞胶原合成。     

湖北、河南、安徽三省大别山区地理新分布植物

湖北、河南、安徽三省大别山区地理新分布植物何家庆（安徽大学生物系合肥２３００３９）关键词大别山区,种子植物,地理新分布ＴＨＥＮＥＷＧＥＯＧＲＡＰＨＩＣＡＬＤＩＳＴＲＩＢＵＴＩＯＮＯＦＳＰＥＲＭＡＴＯＰＨＹＴＥＩＮＤＡＢＩＥＳＨＡＮＴＨＥＲＥＧＩＯＮＳ...     

广东眼镜蛇蛇毒与眼镜王蛇蛇毒冻干粉的鉴别及质量控制的研究 V．广东眼镜蛇蛇毒与眼镜王蛇蛇毒的氨基酸分析

本文采用日立８３５－５０型氨基酸自动分析仪测定了广东眼镜蛇蛇毒与眼镜王蛇蛇毒的氨基酸成分,结果表明两种蛇毒的氨基酸组成基本相同,但多种氨基酸的含量存在明显差异,为蛇毒鉴别和质控提供实验依据。     

以人工合成多肽为抗原的戊型肝炎病毒抗体检测方法的建立和评价

酶联法是ＨＥＶ感染的主要检测方法,多采用基因表达产物为抗原。近来由于人工合成多肽抗原克服了基因重组抗原制备复杂、非特异结构多、难以纯化的缺点,已广泛用于多种病毒感染的检测。根据已发表的ＨＥＶ氨基酸序列的保守性及亲水性等特点,设计合成了两个多肽ＥＳＰ１和ＥＳＰ２,分别位于ＯＲＦ２和ＯＲＦ３区,以此为混合抗原建立了检测ＨＥＶ抗体的间接ＥＬＬＳＡ法,与市售优质试剂比较,其阳性符合率为９７．７５％,阴性符合率为９９．４３％,总符合率为９８．８６％。该方法灵敏度高、特异性强、安全快速,是检测ＨＥＶ感染和流行病学调查的理想方法。     

天然高分子吸附剂研究进展

本文综述了蛋白质、淀粉、甲壳素、纤维素等天然高分子材料作为吸附剂使用的研究进展情况,对它们的制备方法、使用范围和应用前景作了介绍,引用文献122篇。     

金黄色葡萄球菌L型和人乳头瘤病毒与宫颈癌关系的研究

应用改良革兰氏染色和免疫组化染色（ＡＢＣ法）,对２７０例宫颈癌和３３例慢性宫颈炎进行了研究。结果发现,宫颈癌革兰氏染色切片中细菌Ｌ型感染率（７５．１％）明显高于慢性宫颈炎（４５．５％）（Ｐ＜０．０５）,金黄色葡萄球菌Ｌ型抗原阳性率（７６．２％）明显高于人乳头瘤病毒（ＨＰＶ）抗原阳性率（５７．１％）。Ｌ型、ＨＰＶ混合感染率为４２．８％。上述结果表明宫颈癌中金葡菌Ｌ型与ＨＰＶ感染均常见,尤其金葡菌Ｌ型感染更为多见;金葡菌Ｌ型与ＨＰＶ感染的致病特征相似,两者均有不同程度的空泡细胞出现。提示金葡菌Ｌ型感染可能也是宫颈癌的致癌重要因素之一。