Zachariou M, Hearn M T
Centre for Bioprocess Technology, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
J Chromatogr A. 2000 Aug 18;890(1):95-116. doi: 10.1016/s0021-9673(00)00462-3.
In this investigation, human serum has been used as an example of a crude protein mixture to define the protein binding characteristics and selectivity of several immobilised hard Lewis metal ion affinity chromatographic (IMAC) adsorbents. Specifically, the binding properties of immobilised O-phosphoserine (im-OPS) and 8-hydroxyquinoline (im-8-HQ), with immobilised iminodiacetic acid as a control system, have been investigated in combination with the hard Lewis metal ions, Al3+, Ca2+, Fe3+, Yb3+, and the borderline metal ion, Cu2+, over the pH range pH 5.5 to pH 8.0 with buffers of 0.5 M ionic strength. The same IMAC adsorbents were also investigated for their protein binding capabilities with buffers of an ionic strength of 0.06 M at pH 5.5 and pH 8.0. The binding behaviour of four "marker" proteins, namely transferrin, alpha2-macroglobulin, gammaglobulin and human serum albumin have furthermore been employed to monitor the differences in protein selectivity exhibited by these IMAC systems. The experimental findings confirm that these hard Lewis metal ion IMAC adsorbents function in a "mixed" binding mode with both coordination and electrostatic characteristics evident, depending on the ionic strength and pH of the equilibration or elution buffers. Based on a screening protocol, several members of the im-Mn+-8-HQ and im-Mn+-OPS adsorbent series have been identified with high selectivity for transferrin and alpha2-macroglobulin. These hard Lewis metal ion IMAC adsorbents thus provide attractive alternatives for selective fractionation of human serum proteins.
在本研究中,人血清被用作粗蛋白混合物的示例,以定义几种固定化硬路易斯金属离子亲和色谱(IMAC)吸附剂的蛋白质结合特性和选择性。具体而言,以固定化亚氨基二乙酸作为对照体系,研究了固定化O-磷酸丝氨酸(im-OPS)和8-羟基喹啉(im-8-HQ)与硬路易斯金属离子Al3+、Ca2+、Fe3+、Yb3+以及边界金属离子Cu2+在pH 5.5至pH 8.0范围内、离子强度为0.5 M的缓冲液中的结合特性。还研究了相同的IMAC吸附剂在pH 5.5和pH 8.0、离子强度为0.06 M的缓冲液中的蛋白质结合能力。此外,还利用四种“标记”蛋白,即转铁蛋白、α2-巨球蛋白、γ球蛋白和人血清白蛋白的结合行为,来监测这些IMAC系统在蛋白质选择性方面的差异。实验结果证实,这些硬路易斯金属离子IMAC吸附剂以“混合”结合模式起作用,根据平衡或洗脱缓冲液的离子强度和pH值,配位和静电特性均很明显。基于筛选方案,已鉴定出im-Mn+-8-HQ和im-Mn+-OPS吸附剂系列中的几种成员对转铁蛋白和α2-巨球蛋白具有高选择性。因此,这些硬路易斯金属离子IMAC吸附剂为选择性分离人血清蛋白提供了有吸引力的替代方法。