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蛋白质在水溶液中的物理稳定性:非天然蛋白质聚集的机制与驱动力

Physical stability of proteins in aqueous solution: mechanism and driving forces in nonnative protein aggregation.

作者信息

Chi Eva Y, Krishnan Sampathkumar, Randolph Theodore W, Carpenter John F

机构信息

Department of Chemical Engineering, Center for Pharmaceutical Biotechnology, ECCH 111, Campus Box 424, University of Colorado, Boulder, Colorado, USA.

出版信息

Pharm Res. 2003 Sep;20(9):1325-36. doi: 10.1023/a:1025771421906.

DOI:10.1023/a:1025771421906
PMID:14567625
Abstract

Irreversible protein aggregation is problematic in the biotechnology industry, where aggregation is encountered throughout the lifetime of a therapeutic protein, including during refolding, purification, sterilization, shipping, and storage processes. The purpose of the current review is to provide a fundamental understanding of the mechanisms by which proteins aggregate and by which varying solution conditions, such as temperature, pH, salt type, salt concentration, cosolutes, preservatives, and surfactants, affect this process.

摘要

不可逆蛋白质聚集在生物技术行业中是个问题,在治疗性蛋白质的整个生命周期中都会遇到聚集现象,包括在重折叠、纯化、灭菌、运输和储存过程中。本综述的目的是对蛋白质聚集的机制以及不同的溶液条件(如温度、pH值、盐类型、盐浓度、共溶质、防腐剂和表面活性剂)如何影响这一过程提供基本的理解。

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本文引用的文献

1
[6] Second virial coefficient as predictor in protein crystal growth.[6] 作为蛋白质晶体生长预测指标的第二维里系数。
Methods Enzymol. 1997;276:100-110. doi: 10.1016/S0076-6879(97)76052-X.
2
Theoretical analysis of Lumry-Eyring models in differential scanning calorimetry.差示扫描量热法中 Lumry-Eyring 模型的理论分析。
Biophys J. 1992 Apr;61(4):921-35. doi: 10.1016/S0006-3495(92)81899-4.
3
Structure dynamics of proteins by hydrogen exchange methods.通过氢交换方法研究蛋白质的结构动力学
热处理对豌豆和大豆蛋白基乳液及其喷雾干燥粉末的物理化学、界面和包封性能的影响。
Food Chem X. 2025 Jul 14;29:102791. doi: 10.1016/j.fochx.2025.102791. eCollection 2025 Jul.
4
Exploring Protein Aggregation in Biological Products: From Mechanistic Understanding to Practical Solutions.探索生物制品中的蛋白质聚集:从机理理解到实际解决方案
AAPS PharmSciTech. 2025 Jul 8;26(6):189. doi: 10.1208/s12249-025-03189-2.
5
Impact of Initial Aggregate Level on Aggregation Potential of Monoclonal Antibodies in Different Buffer Systems.初始聚集体水平对不同缓冲体系中单克隆抗体聚集潜力的影响
Pharm Res. 2025 Jun 6. doi: 10.1007/s11095-025-03874-8.
6
Assessment of biophysical properties of the first-in-class anti-cancer IgE antibody drug MOv18 IgE demonstrates monomeric purity and stability.一流抗癌IgE抗体药物MOv18 IgE的生物物理特性评估表明其具有单体纯度和稳定性。
MAbs. 2025 Dec;17(1):2512211. doi: 10.1080/19420862.2025.2512211. Epub 2025 May 28.
7
Competitive adsorption of a monoclonal antibody and amphiphilic polymers to the air-water interface.单克隆抗体与两亲性聚合物在气-水界面的竞争吸附。
Eur Biophys J. 2025 May 22. doi: 10.1007/s00249-025-01752-0.
8
The effect of mepolizumab dosage form on treatment outcomes in severe asthma.美泊利珠单抗剂型对重度哮喘治疗结果的影响。
Front Med (Lausanne). 2025 Apr 17;12:1537074. doi: 10.3389/fmed.2025.1537074. eCollection 2025.
9
Comparative Forced Degradation Study of Anticomplement C5 Biosimilar and Originator Monoclonal Antibodies.抗补体C5生物类似药与原研单克隆抗体的比较强制降解研究
Pharmaceuticals (Basel). 2025 Apr 16;18(4):579. doi: 10.3390/ph18040579.
10
Unraveling the Effects of Filtration, Process Interruptions, and Post-Process Agitation on Protein Aggregation.解析过滤、工艺中断及工艺后搅拌对蛋白质聚集的影响。
AAPS PharmSciTech. 2025 Mar 14;26(3):85. doi: 10.1208/s12249-025-03076-w.
Biophys J. 1980 Oct;32(1):619-21. doi: 10.1016/S0006-3495(80)84994-0.
4
On the role of reversible denaturation (unfolding) in the irreversible thermal inactivation of enzymes.论可逆变性(解折叠)在酶的不可逆热失活中的作用。
Biotechnol Bioeng. 1983 Sep;25(9):2221-30. doi: 10.1002/bit.260250908.
5
Predicting protein crystallization from a dilute solution property.从稀溶液性质预测蛋白质结晶。
Acta Crystallogr D Biol Crystallogr. 1994 Jul 1;50(Pt 4):361-5. doi: 10.1107/S0907444994001216.
6
Use of glycerol, polyols and other protein structure stabilizing agents in protein crystallization.甘油、多元醇及其他蛋白质结构稳定剂在蛋白质结晶中的应用。
Acta Crystallogr D Biol Crystallogr. 1995 May 1;51(Pt 3):271-7. doi: 10.1107/S0907444994014009.
7
Roles of conformational stability and colloidal stability in the aggregation of recombinant human granulocyte colony-stimulating factor.构象稳定性和胶体稳定性在重组人粒细胞集落刺激因子聚集过程中的作用
Protein Sci. 2003 May;12(5):903-13. doi: 10.1110/ps.0235703.
8
Oxidative dimer formation is the critical rate-limiting step for Parkinson's disease alpha-synuclein fibrillogenesis.氧化二聚体形成是帕金森病α-突触核蛋白纤维形成的关键限速步骤。
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9
A kinetic study of beta-lactoglobulin amyloid fibril formation promoted by urea.尿素促进β-乳球蛋白淀粉样纤维形成的动力学研究。
Protein Sci. 2002 Oct;11(10):2417-26. doi: 10.1110/ps.0217702.
10
Stabilization of proteins by low molecular weight multi-ions.低分子量多离子对蛋白质的稳定作用。
J Pharm Sci. 2002 Oct;91(10):2220-9. doi: 10.1002/jps.10219.