几种阳离子卟啉的生物学活性研究

发布时间：2018-01-06 00:26

  本文关键词：几种阳离子卟啉的生物学活性研究　出处：《武汉大学》2005年博士论文　论文类型：学位论文

  更多相关文章： 阳离子卟啉 核酸 蛋白质 生物学活性 阿霉素

【摘要】：卟啉不仅以其独特的生物活性存在于自然界,而且因其结构具有奇异的性能与癌细胞有特殊的亲合力,在医学研究中可作为检测癌症的光敏剂和抗癌药物。其中阳离子卟啉由于具有核酸的结合和切割特性,吸引了人们极大的兴趣。本文从合成和应用研究中经常使用的阳离子卟啉出发,包括5,10,15,20—四(1—甲基—4—吡啶基)卟啉甲苯磺酰盐(TMPyP)和5,10,15,20—四(1—乙氧羰基甲基—4—吡啶基)卟啉四氯盐(H_2TEOCMPyP)及其金属配合物,研究了亲水性阳离子卟啉与蛋白质和核酸的相互作用,探讨了它们在转运、肿瘤选择性及DNA损伤方面的相关特性。在此基础上,为提高其性能,改变了1—2个侧链基团,合成了3种新型阳离子卟啉化合物,进一步研究了它们的抗微生物和抗肿瘤活性。测试了几种新型卟啉对DNA的结合和损伤作用,并对比了它们与临床常用的癌症化疗药物阿霉素(ADM)对脂质体的过氧化损伤作用,从分子水平对卟啉的抗微生物和抗肿瘤机制进行了初步探讨。 本文的工作内容和结果总结如下: 结合荧光光谱和吸收光谱,研究了卟啉与人血清白蛋白(HSA)的相互作用,确定了反应的结合常数和授体-受体间的结合距离;采用光学生物传感器法获得卟啉与固定化HSA相互作用的动力学与热力学常数,比较了25℃时该方法与荧光光谱法得到的结合常数,发现两种方法具有可比性。卟啉主要通过静电相互作用与HSA结合,结合常数在10~5L/mol左右,金属和侧链的疏水性对卟啉与HSA的亲合力有影响,疏水作用力仍在一定程度上发挥作用。卟啉结合在HSA疏水腔外部,与疏水腔保持一定的距离。 应用IAsys光学生物传感器研究了两种水溶性阳离子卟啉与固定化的麦胚凝集素(WGA)的相互作用。20℃时自由卟啉和相应的锌卟啉的结合常数分别为
[Abstract]:Porphyrins not only exist in nature because of their unique biological activity, but also have special affinity with cancer cells because of their unique properties. In medical research, it can be used as Guang Min's agent and anticancer drug for cancer detection, among which cationic porphyrin has the characteristics of nucleic acid binding and cleavage. In this paper, cationic porphyrins, which are often used in synthesis and application research, are studied, including 5Cationic porphyrins. TMPyP) and 5H101015 (TMPyP15) of porphyrin toluenesulfonyl salt (TMPyP15) and tetra-tetrachloro-1-methyl-4-pyridyl) porphyrin. The interaction of hydrophilic cationic porphyrin with protein and nucleic acid was studied. In order to improve their properties, three new cationic porphyrin compounds were synthesized in order to improve their properties by changing 1-2 side chain groups. Their antimicrobial and antitumor activities were further studied. The binding and damage effects of several new porphyrins on DNA were tested. The effects of adriamycin and adriamycin on the peroxidation of liposomes were compared, and the anti-microbial and anti-tumor mechanisms of porphyrin were discussed at molecular level. The contents and results of this paper are summarized as follows: The interaction of porphyrin with human serum albumin (HSA) was studied by fluorescence spectra and absorption spectra. The binding constants of the reaction and the binding distance between donor and acceptor were determined. The kinetic and thermodynamic constants of the interaction between porphyrin and immobilized HSA were obtained by optical biosensor method. It is found that the two methods are comparable. Porphyrin binds to HSA mainly by electrostatic interaction with a binding constant of about 10 ~ 5 L / mol. The hydrophobicity of metal and side chain has an effect on the affinity of porphyrin to HSA, and the hydrophobic force still exerts its effect to some extent. Porphyrin binds outside the hydrophobic cavity of HSA and keeps a certain distance from the hydrophobic cavity. Two kinds of water-soluble cationic porphyrin and immobilized wheat germ agglutinin were studied by IAsys optical biosensor. The binding constants of free porphyrin and zinc porphyrin at 20 鈩，

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