A MATHEMATICAL-MODEL TO PREDICT THE PARTITIONING OF PEPTIDES AND PEPTIDE-MODIFIED PROTEINS IN AQUEOUS 2-PHASE SYSTEMS
A MATHEMATICAL-MODEL TO PREDICT THE PARTITIONING OF PEPTIDES AND PEPTIDE-MODIFIED PROTEINS IN AQUEOUS 2-PHASE SYSTEMS
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DOI：
10.1021/bp00029a009
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发表时间：
1994-09-01
影响因子：
2.9
通讯作者：
VEIDE, A
中科院分区：
文献类型：
--
作者：
EITEMAN, MA;HASSINEN, C;VEIDE, A
开发了一种数学程序来根据氨基酸疏水性预测肽 AIIP、AWWP、AIIPAIIP 和 AWWPAWWP 在聚乙二醇 (PEG)/磷酸盐水性两相系统中的分配系数。一般来说，含有色氨酸的肽比含有异亮氨酸的类似肽更多地分配到富含 PEG 的上相中。具体来说，随着 PEG/磷酸钾水性两相系统中各相之间 PEG 浓度差的增加，观察到肽 AIIP 的分配系数为 1.2 至 1.6，AIIPAIIP 为 2.4 至 5.7，AWWP 从 13.5 至 32.2，AWWPAWWP 从 43 至 170。该模型被扩展以预测葡萄球菌蛋白 A 的分配用这四种肽修饰的衍生物（ZZ）。正如预测的那样，用含异亮氨酸的肽修饰的蛋白质比用含色氨酸的肽修饰的蛋白质具有更低的分配系数。在这些系统中，ZZ蛋白的分配系数为0.35至0.20，ZZAIIPAIIP的分配系数为0.58至0.48，ZZAWWPAWWP的分配系数为3.5至5.3。结果表明，短肽手柄可以显着增强蛋白质在水性两相系统中的分配。还讨论了模型与肽手柄的表面暴露之间的关系，以及该模型在帮助设计此类手柄以增强纯化方面的效用。
A mathematical procedure was developed to predict the partition coefficients of the peptides AIIP, AWWP, AIIPAIIP and AWWPAWWP in poly(ethylene glycol) (PEG)/phosphate aqueous two-phase systems from amino acid hydrophobicities. In general, peptides containing tryptophan partition more into the PEG-enriched upper phase than analogous peptides containing isoleucine. Specifically, as the PEG concentration difference between the phases increased in a PEG/potassium phosphate aqueous two-phase system, the peptide AIIP was observed to have a partition coefficient ranging from 1.2 to 1.6, AIIPAIIP from 2.4 to 5.7, AWWP from 13.5 to 32.2, and AWWPAWWP from 43 to 170. The model was extended to predict the partitioning of a staphylococcal protein A derivative (ZZ) modified with these four peptides. As predicted,the protein modified with isoleucine-containing peptides had lower partition coefficients than the protein modified with tryptophan-containing peptides. The partition coefficient of the ZZ protein ranged from 0.35 to 0.20, that of ZZAIIPAIIP from 0.58 to 0.48, and that of ZZAWWPAWWP from 3.5 to 5.3 in these systems. The results show that short peptide handles can significantly enhance the partitioning of proteins in aqueous two-phase systems. The relationship between the model and the surface exposure of peptide handles and the utility of the model to aid in the design of such handles to enhance purifications are also discussed.