3,4-亚甲二氧苯基甲酰吗啉与AMPA受体的结合作用研究

Study of 3,4-Methylenedioxyphenyl Formylmorpholine Binding to AMPA Receptor

目的研究3,4-亚甲二氧苯基甲酰吗啉(化合物1)与AMPA受体的结合作用。方法采用放射性配体受体结合试验测定化合物1与AMPA受体结合的IC50值;采用分子对接技术研究化合物1与AMPA受体的结合能力和结合模式。结果化合物1与AMPA受体结合的IC50值为1.74×10^(-9)mol·L^(-1),具有较强的结合能力;化合物1与AMPA受体的结合能为-5.46 kcal·mol^(-1),同样表明结合能力较强。结合的驱动力主要是氢键、疏水作用和静电作用。化合物1结构中O原子可与AMPA受体的Ser108、Ser242氨基酸残基形成氢键,这可能是该化合物与AMPA受体结合的重要位点。结论化合物1可与AMPA结合,且结合能力较强。

OBJECTIVE To investigate the binding of 3,4-methylenedioxyphenyl formylmorpholine(compound 1)to AMPA receptor.METHODS The potency of compound 1 binding to AMPA receptor was evaluated by radioligand binding assay.Meanwhile,the binding mode of compound 1 to AMPA receptor was evaluated by molecular docking.RESULTS Compound 1 showed high affinity of AMPA receptor with the IC50 value of 1.74×10-9 mol·L-1.Meanwhile,the results from molecular docking indicated that compound 1 could bind to AMPA receptor by high affinity with theΔE value of-5.46 kcal·mol-1.Hydrogen bond,hydrophobic force and electrostatic interaction played key roles in binding.Moreover,the O atoms of compound 1 could form hydrogen bond with Ser108 and Ser242 of AMPA receptor,which was recommended as the key binding site.CONCLUSION The results demonstrate that compound 1 could bind to AMPA receptor with high affinity,.