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有机化学
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有机化学 ›› 2010, Vol. 30 ›› Issue (10): 1492-1496. 上一篇    下一篇

研究论文

电化学活性的二茂铁-肽的合成及其对β-淀粉样肽聚集的抑制作用

李学强，魏传晚，刘晓芳，刘又年   

  1. (中南大学化学化工学院 长沙 410083)
  • 收稿日期:2010-02-20 修回日期:2010-03-06 发布日期:2010-05-12
  • 通讯作者: 刘又年 E-mail:liuyoun@csu.edu.cn
  • 基金资助:

    国家自然科学基金

Synthesis of Ferrocenoyl-peptide and Its Inhibition for β-Amyloid Peptide

LI Xue-Qiang, WEI Chuan-Wan, LIU Xiao-Fang, LIU You-Nian   

  1. (College of Chemistry and Chemical Engineering, Central South University, Changsha 410083)
  • Received:2010-02-20 Revised:2010-03-06 Published:2010-05-12
  • Contact: You-Nian LIU E-mail:liuyoun@csu.edu.cn

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以二茂铁甲酸、甘氨酸、苯丙氨酸、亮氨酸、缬氨酸和赖氨酸为原料, 苯并三唑-1-四甲基六氟磷酸酯(HBTU)及1-羟基苯并三唑(HOBt)为缩合剂, 采用固相合成法, 合成了Fc-Gly-Lys-Leu-Val-Phe-Phe-Gly-Lys-OH(简称Fc- GKLVFFGK, 其中Fc: ferrocenoyl, 二茂铁). 用HPLC分离纯化得到目标化合物, 并对目标化合物进行红外、紫外、核磁和质谱表征确证其结构. Fc-GKLVFFGK的循环伏安扫描结果表明, 在0.2～0.7 V范围内出现了一对可逆的氧化还原峰, 氧化峰和还原峰电位分别为0.464和0.396 V|峰电位之差?Ep为58 mV, 峰电流密度之比Ipa/Ipc＝1.07. 采用ThT 荧光探针法检测了Fc-GKLVFFGK对β-淀粉样肽(Aβ)聚集的抑制作用. 实验结果表明, Fc-GKLVFFGK能有效地抑制Aβ1-42聚集, 并且能有效地分解已形成的Aβ1-42纤维.

关键词: 二茂铁-肽, 固相合成, 电化学特性

Fc-Gly-Lys-Leu-Val-Phe-Phe-Gly-Lys-OH (Fc-GKLVFFGK, Fc: ferrocenoyl) was synthesized from ferrocene monocarboxylic acid, Gly, Phe, Leu Val and Lys by solid-phase peptide synthesis method using O-(benzotriazol-yl)-N,N,N ,N -tetramethyluronium (HBTU)/1-hydroxybenzotrizole (HOBT) as coupling reagents. The crude peptide was purified by HPLC. The title peptide, Fc-Gly-Lys-Leu-Val-Phe-Phe- Gly-Lys-OH (Fc-GKLVFFGK), was then characterized by IR, UV, NMR and MS techniques. The voltammetric method was employed to determine the electrochemi-cal properties of the title compound. The electrochemical results showed that the title compound exhibit a pair of well-defined redox wave at oxidation potential (Ea) and reduction potential (Ec) at 0.464 and 0.396 V, respectively, in the range of 0.2～0.7 V, and the ratio of Ipa and Ipc is 1.07. The inhibitory properties of Fc-GKLVFFGK for the aggregation of β-amyloid peptide (Aβ1-42) were investigated by thiofla-vin T (ThT) fluorescence spectroscopy in vitro. The experimental results showed that the inhibitory effect of the ferrocene attached GKLVFFGK for the aggregation of Aβ1-42 is better than that of KLVFF itself. Moreover, Fc-GKLVFFGK is able to partially disaggregate performed Aβ fi-brils.

Key words: ferrocenoyl peptide, solid phase peptide synthesis, electrochemical property