Biotherapeutic protein formulation variables influence protein integrity and can promote post-translational modifications as shown using chicken egg white lysozyme as a model system.
Biotherapeutic protein formulation variables influence protein integrity and can promote post-translational modifications as shown using chicken egg white lysozyme as a model system.
复制标题
DOI：
10.1007/s10529-015-2014-y
复制
发表时间：
2016-04
影响因子：
2.7
通讯作者：
Smales CM
中科院分区：
文献类型：
--
作者：
Gourbatsi E;Povey J;Uddin S;Smales CM
以溶菌酶为模型蛋白，研究了不同配方变量对蛋白质完整性的影响，以开发用于临床的生物治疗蛋白配方。缓冲液的组成/浓度是决定溶菌酶稳定性和真实性的关键变量，与蛋白质浓度无关，而储存温度和时间也同样是关键变量。该蛋白的色氨酸图谱显示，在特定条件下配方时发生修饰，而不是在其他条件下。建立了一个模型肽体系，在制剂条件下反映了与完整溶菌酶相同的行为。肽模型可以反映相同配方中蛋白质或蛋白质区域的稳定性，并可用于帮助开发用于稳定生物治疗蛋白质的配方的快速筛选。本文的在线版本（doi:10.1007/s10529-015-2014-y）含有补充资料，仅供授权用户使用。
The effect of different formulations variables on protein integrity were investigated using lysozyme as a model protein for the development of biotherapeutic protein formulations for use in the clinic. Buffer composition/concentration was the key variable of formulation reagents investigated in determining lysozyme stability and authenticity independent of protein concentration whilst the storage temperature and time, not surprisingly, were also key variables. Tryptic peptide mapping of the protein showed that the modifications occurred when formulated under specific conditions but not others. A model peptide system was developed that reflected the same behavior under formulation conditions as intact lysozyme. Peptide models may mirror the stability of proteins, or regions of proteins, in the same formulations and be used to help develop a rapid screen of formulations for stabilisation of biotherapeutic proteins. The online version of this article (doi:10.1007/s10529-015-2014-y) contains supplementary material, which is available to authorized users.