Fc-L-Pro-L-Leu-Gly-OMe二茂铁—肽的合成、结构分析及其电化学性质

【作者】 向进；

【导师】 刘又年；

【作者基本信息】 中南大学 ， 无机化学， 2010， 硕士

【摘要】 二茂铁(Ferrocene, Fc)是一类富电子化合物,具有良好的电化学活性,且二茂铁基团具有亲脂性、氧化还原活性、稳定性及低毒性。因此二茂铁的衍生物具有优良的电化学和生物活性,在生物、医学、微生物学等方面已得到广泛应用。PLG是一种小分子三肽,即L-脯氨酸-L-亮氨酸-L-甘氨酸(L-Prolyl-L-Leucyl-Gly-OMe),它又称为促黑激素的抑制激素(Melanocyte stimulating hormone-inhibiting hormone, MIF-1),可抑制黑色素细胞刺激释放因子(Melanocyte Stimulating Hormone, MSH)的释放。大量临床实验证实,PLG可用于治疗帕金森氏症。以二茂铁甲酸、Pro、Leu、和Gly为起始原料,采用液相合成法,以HBTU和HOBt为缩合剂,将具有电化学活性的二茂铁和具有治疗帕金森氏症的PLG多肽耦联,合成了两种新的二茂铁-肽分子Fc-Pro-Leu-Gly-OMe和Fc-Pro-Leu-Gly-NH2,得到的产物产率分别为：31%,25%。采用X-ray衍射法在-100℃解析其晶体结构,得到的Fc-PLG-OMe晶体属于单斜晶系,空间点群为C2,晶包参数为：a=20.803(3)A,b=6.4428(4)A,c=20.557(2)A,α=90°,β=115.498(5),γ=90°,Z=4,R=0.0451；两个二茂铁环形成的二面角为178.41(4)°,被取代的二茂铁环与脯氨酸环形成的二面角为14.0°,在甘氨酸的N13和脯氨酸的O11之间形成强烈的氢键(d(N-O)=2.835A)使得整个分子形成一个β-turn的结构。采用循环伏安法对Fc-PLG在甲醇溶液中的电化学性质进行了检测,氧化峰和还原峰分别为0.475 V和0.392 V,峰电流密度之比为iPa/iPc=1.012,峰电位之差ΔEp=83 mV。并证明了Fc-PLG在甲醇溶液中的电化学行为是一种单电子转移的准可逆过程。更多还原

【Abstract】 Ferrocene and its derivatives due to their biological activity, high lipophhilicity, redox activity, stability, low cytotoxicity and distinctive electrochemical behavior have been widely used in biology, medicine and microbiology.PLG (L-Prolyl-L-Leucyl-Gly-OMe) is an endogenous tripeptide found in the central nervous system, it is also known as melanocyte-stimulating release inhibiting factor-1 (MIF-1). It can control the release of melanocyte-stimulating hormone (MSH). A number of clinical studies have showed that PLG possessed substantial therapeutic activities in Parkinson’s disease.Firstly, the ferrocene conjugates Fc-Pro-Leu-Gly-OMe and Fc-Pro-Leu-Gly-NH2 were synthesized from ferrocene, proline, leucine, glysine acid by liquid phase synthesis, using HBTU and HOBt as coupling agents. The structure of the compound was characterized by IR-spectrum, UV-vis spectrum,1H NMR and ESI-MS. Their yields were 31% and 25%.Secondly, The Fc-PLG crystal structure was analytical at-100℃by diffraction. The crystal was monoclinic, space group C2 with the cell parameter is a=20.803(3) A, b=6.4428(4) A, c=20.557(2) A, a=90°,β=115.498(5)°, y=90°,Z=4, R=0.0451. The twist angle between Cp rings is 178.4°,the amide plane is rotated out of the Cp ring plane by 14.1°. A strong hydrogen bond between the Gly amide nitrogen N13 and Pro amide oxygen is typical for the structure motif of a P-turn. (d(N-O)=2.835A).A method of CV (Cyclic Voltammetry) was carried out to observe the electrochemical properties of Fc-Pro-Leu-Gly-OMe and it was proved that it was a quasireversible electrochemical process in methanol, the oxidation potential (Ea) and reduction potential (Ec) were observed at 0.475 V and 0.372 V, The oxidation peak shifted about 83 mV to anodic and the ratio of ipa and ipc was 1.012.更多还原