L-酪氨酸衍生物的合成及其与人血清白蛋白的相互作用

Syntheses of L-Tyrosine Derivatives and Their Interaction with Human Serum Albumin

以L-酪氨酸为原料,分别与邻甲氧基肉桂酸和间甲氧基肉桂酸进行了酰胺化反应,合成了两种L-酪氨酸衍生物(E)-3-(4'-羟基苯基)-2-[3″-(2-甲氧基苯基)丙烯酰胺基]丙酸(I)和(E)-3-(4'-羟基苯基)-2-[3″-(3-甲氧基苯基)丙烯酰胺基]丙酸(II),运用ESI-MS、1H NMR、13C NMR对其结构进行表征确认。通过荧光光谱、紫外可见吸收光谱结合Auto Dock分子对接方法,研究了化合物I和II对人血清白蛋白(HSA)的作用机制。结果表明,I和II对HSA的猝灭机制为静态猝灭,过程中伴随着非辐射能量转移。化合物I和II主要通过疏水作用与HSA的结合,结合过程是自发的。Auto Dock分子对接结果表明化合物I和II与HSA之间主要是疏水作用力,结合位点位于亚结构域IIA形成的疏水腔中,即site I。分子对接结果与光谱实验结果基本一致。

Two L-tyrosine derivatives,（ E）-3-（ 4＇-hydroxyphenyl）-2-[3″-（ 2-methoxyphenyl） acrylamido]propanoic acid（ I） and（ E）-3-（ 4＇-hydroxyphenyl）-2-[3″-（ 3-methoxyphenyl） acrylamido]propanoic acid（ II）,were synthesized from o-methoxycinnamic acid and m-methoxycinnamic acid respectively. Their structures were characterized by ESI-MS,1H NMR and13 C NMR. The mechanism of the interaction between derivatives and human serum albumin（ HSA） was researched by the fluorescence emission spectra,synchronous fluorescence spectra,UVVis spectra and molecular docking. The results indicated that the quenching mechanism of derivatives and HSA was static. The process was accompanied with the non-radiative energy transfer. Hydrophobic interaction was the predominant intermolecular force in the combination of derivatives and HSA. The process was spontaneous. Molecular docking showed that the hydrophobic cavity of the subdomain IIA（ site I） was the location of the binding site of derivative I / II and HSA. Hydrophobic interaction contributed to their combination,which was consistent with the experimental results.