人白蛋白与3-氨甲基吡啶相互作用的研究  

Study on interaction between human albumin and 3-amino methyl pyridine

作　　者：杨金菊[1] 王继武 李永红[3] 戴平[1] 李荣秀[3] 

机构地区：[1]华东师范大学生命科学学院,上海200062 [2]上海市转基因研究中心,上海201303 [3]中国科学院上海生命科学研究院上海生物工程研究中心,上海200233

出　　处：《中国药学杂志》2003年第11期882-885,共4页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目 (3 9980 0 3 2 );国家高技术研究发展计划经费资助项目(Z2 1-0 4-0 5和 10 3 -13 -0 3 -0 7)

摘　　要：目的　研究人白蛋白与 3 氨甲基吡啶 (潜在的亲和配体 )之间的相互作用规律。方法　在不同酸碱度和盐浓度的缓冲液条件下将固定化 3 氨甲基吡啶与人血浆中的白蛋白接触 ,测定 3 氨甲基吡啶对人白蛋白的结合量。用亲和毛细管电泳方法测定了液相状态下白蛋白与 3 氨甲基吡啶相互作用的亲和常数及结合位点的数目 ,并与固相状态下的作用机制进行了比较。最后用计算机辅助分子模拟的方法 ,在白蛋白三级结构上搜寻可能的结合位点 ,结合实验数据阐明相互作用的机制。结果　在 pH8.0时结合量最高 ,并随 pH升高和降低而减少 ;结合的量随盐浓度的增大而减少 ,潜在结合口袋区域存在ASP2 5 6 ,ASP2 5 9两个带电荷的氨基酸残基。结论　静电相互作用是白蛋白与 3 氨甲基吡啶的结合的主要动力 ,吡啶环的疏水性质和空间体积的排斥性质可能决定了白蛋白与 3 氨甲基吡啶相互作用的专一性。OBJECTIVE: To study the interaction between human albumin and the affinity ligand 3-amino methyl pyridine. METHODS: Immobilized 3-aminomethyl pyridine was contacted with albumin in human plasma under buffered solutions at different pHs and concentrations of salt. The amount of albumin bound was analyzed. In addition, the affirity constants of human albumin and the free ligand and immobilized ligand were measured. Computer-aided molecular modeling was used to search the potential binding site on the surface of albumin, and the interaction was scrutinized with the properties of functional chemical groups at the binding site of amino acid. RESULTS: Albumin binding capacity reached peak at pH8. 0, and decreased with pH increasing or decreasing. The binding capacity decreased when increasing salt concentration. Two charged groups of ASP256 and ASP259 at the potential binding site were found. CONCLUSION: Electrostatic interactions appeared to be the primary interactions between human albumin and 3-amino methyl pyridine. Hydrophobic nature and steric hindrance of pyridine probably contribute to the recognition specificity.

关 键 词：白蛋白 3-氨甲基吡啶 相互作用 亲和常数 

分 类 号：R917[医药卫生—药物分析学]