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    • 9. 发明专利
    • Protein surface remodeling
    • 蛋白表面重构
    • JP2013063093A
    • 2013-04-11
    • JP2013004389
    • 2013-01-15
    • President & Fellows Of Harvard Collegeプレジデント アンド フェロウズ オブ ハーバード カレッジPresident and Fellows of Harvard College
    • LIU DAVID RPHILLIPS KEVIN JOHNLAWRENCE MICHAEL S
    • C12N15/09C07K14/00
    • Y02P20/52
    • PROBLEM TO BE SOLVED: To provide a system for routinely modifying proteins to be more stable and/or to prevent aggregation.SOLUTION: The major cause of misbehavior of proteins is aggregation. The system for modifying the protein to create a more stable variant is provided. The method involves a step of identifying non-conserved hydrophobic amino acid residues on the surface of a protein, suitable for mutating to more hydrophilic residues (e.g. charged amino acids). Any number of residues on the surface may be changed to create a variant that is more soluble, resistant to aggregation, has a greater ability to re-fold, and/or is more stable under a variety of conditions. The invention also provides GFP, streptavidin, and GST variants with an increased theoretical net charge created by the inventive technology. Kits are also provided for carrying out such modifications on any protein of interest.
    • 要解决的问题:提供用于常规修饰蛋白质以更稳定和/或防止聚集的系统。 解决方案:蛋白质不正常的主要原因是聚集。 提供了用于修饰蛋白质以产生更稳定变体的系统。 该方法包括鉴定蛋白质表面上的非保守疏水性氨基酸残基的步骤,适用于突变为更亲水残基(例如带电氨基酸)。 可以改变表面上的任何数量的残基,以产生更可溶,耐聚集,更大的再折叠能力和/或在各种条件下更稳定的变体。 本发明还提供具有由本发明技术产生的增加的理论净电荷的GFP,链霉抗生物素蛋白和GST变体。 还提供了用于对任何感兴趣的蛋白进行这些修饰的试剂盒。 版权所有(C)2013,JPO&INPIT