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  

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

作　　者：李学强[1] 魏传晚[1] 刘晓芳[1] 刘又年[1] 

机构地区：[1]中南大学化学化工学院,长沙410083

出　　处：《有机化学》2010年第10期1492-1496,共5页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(No.20876179)资助项目

摘　　要：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0.2～0.7V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0.396V;峰电位之差?Ep为58mV,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.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 electrochemical 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 thioflavin 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 fibrils.

关 键 词：二茂铁-肽 固相合成 电化学特性 

分 类 号：R749.16[医药卫生—神经病学与精神病学]