Arakawa Tsutomu, Futatsumori-Sugai Mutsumi, Tsumoto Kouhei, Kita Yoshiko, Sato Haruna, Ejima Daisuke
Alliance Protein Laboratories, Thousand Oaks, CA 91360, USA.
Protein Expr Purif. 2010 Jun;71(2):168-73. doi: 10.1016/j.pep.2009.11.004. Epub 2009 Nov 12.
Binding, washing and elution conditions for MEP HyperCel chromatography were examined using two conditioned media (CM) containing monoclonal antibodies (humanized IgG1) and bovine serum albumin (BSA). Monoclonal antibodies derived from mammalian expression system bound to the column without pretreatment, although a majority of contaminating proteins present in the CM also showed binding. Inorganic salts, ethanol and glycerol were ineffective in eluting proteins under the conditions examined, suggesting that electrostatic or hydrophobic interactions are not a major factor for antibody binding to the MEP resin. Ethylene glycol, 2-propanol, urea and arginine were effective, to varying degrees, in elution of the bound proteins. The bound contaminating proteins and BSA were effectively eluted with ethylene glycol and the bound antibodies were finally eluted with aqueous arginine solutions at neutral pH. MEP showed selectivity toward BSA and hence utility for removing BSA from the samples. Interestingly, Fc-fusion proteins derived from silkworm larvae showed no detectable binding. Serum proteins present in silkworm larvae strongly competed with the Fc-fusion proteins and monoclonal antibody for binding to MEP resin, while the same Fc-fusion proteins can be readily purified in one-step by Protein-A resin, again confirming weak selectivity of the MEP resin.
使用两种含有单克隆抗体(人源化IgG1)和牛血清白蛋白(BSA)的条件培养基(CM),研究了MEP HyperCel色谱的结合、洗涤和洗脱条件。源自哺乳动物表达系统的单克隆抗体无需预处理即可与柱结合,尽管CM中存在的大多数污染蛋白也显示出结合。在所研究的条件下,无机盐、乙醇和甘油在洗脱蛋白质方面无效,这表明静电或疏水相互作用不是抗体与MEP树脂结合的主要因素。乙二醇、2-丙醇、尿素和精氨酸在不同程度上有效地洗脱了结合的蛋白质。结合的污染蛋白和BSA用乙二醇有效洗脱,结合的抗体最终用中性pH的精氨酸水溶液洗脱。MEP对BSA具有选择性,因此可用于从样品中去除BSA。有趣的是,源自家蚕幼虫的Fc融合蛋白未显示出可检测到的结合。家蚕幼虫中存在的血清蛋白与Fc融合蛋白和单克隆抗体强烈竞争与MEP树脂的结合,而相同的Fc融合蛋白可以通过Protein-A树脂一步轻松纯化,这再次证实了MEP树脂的弱选择性。