本文關鍵詞：幾種陽離子卟啉的生物學活性研究　出處：《武漢大學》2005年博士論文　論文類型：學位論文

  更多相關文章： 陽離子卟啉 核酸 蛋白質(zhì) 生物學活性 阿霉素

【摘要】：卟啉不僅以其獨特的生物活性存在于自然界,而且因其結構具有奇異的性能與癌細胞有特殊的親合力,在醫(yī)學研究中可作為檢測癌癥的光敏劑和抗癌藥物。其中陽離子卟啉由于具有核酸的結合和切割特性,吸引了人們極大的興趣。本文從合成和應用研究中經(jīng)常使用的陽離子卟啉出發(fā),包括5,10,15,20—四(1—甲基—4—吡啶基)卟啉甲苯磺酰鹽(TMPyP)和5,10,15,20—四(1—乙氧羰基甲基—4—吡啶基)卟啉四氯鹽(H_2TEOCMPyP)及其金屬配合物,研究了親水性陽離子卟啉與蛋白質(zhì)和核酸的相互作用,探討了它們在轉(zhuǎn)運、腫瘤選擇性及DNA損傷方面的相關特性。在此基礎上,為提高其性能,改變了1—2個側(cè)鏈基團,合成了3種新型陽離子卟啉化合物,進一步研究了它們的抗微生物和抗腫瘤活性。測試了幾種新型卟啉對DNA的結合和損傷作用,并對比了它們與臨床常用的癌癥化療藥物阿霉素(ADM)對脂質(zhì)體的過氧化損傷作用,從分子水平對卟啉的抗微生物和抗腫瘤機制進行了初步探討。 本文的工作內(nèi)容和結果總結如下: 結合熒光光譜和吸收光譜,研究了卟啉與人血清白蛋白(HSA)的相互作用,確定了反應的結合常數(shù)和授體-受體間的結合距離;采用光學生物傳感器法獲得卟啉與固定化HSA相互作用的動力學與熱力學常數(shù),比較了25℃時該方法與熒光光譜法得到的結合常數(shù),發(fā)現(xiàn)兩種方法具有可比性。卟啉主要通過靜電相互作用與HSA結合,結合常數(shù)在10~5L/mol左右,金屬和側(cè)鏈的疏水性對卟啉與HSA的親合力有影響,疏水作用力仍在一定程度上發(fā)揮作用。卟啉結合在HSA疏水腔外部,與疏水腔保持一定的距離。 應用IAsys光學生物傳感器研究了兩種水溶性陽離子卟啉與固定化的麥胚凝集素(WGA)的相互作用。20℃時自由卟啉和相應的鋅卟啉的結合常數(shù)分別為
[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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