中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Mechanism of bio-macromolecule denaturation on solid-liquid surface of ion-exchange chromatographic media - A case study for inactivated foot-and-mouth disease virus

文献类型:期刊论文

作者Yang, Yanli1; Song, Yanmin1,2; Lin, Xuan1,2; Li, Shuai1,2; Li, Zhengjun1; Zhao, Qizu3; Ma, Guanghui1; Zhang, Songping1; Su, Zhiguo1
刊名JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
出版日期2020-04-01
卷号1142页码:10
关键词Differential scanning calorimetry Solid-liquid interface Ion exchange chromatography Foot-and-mouth disease virus Dissociation Stability
ISSN号1570-0232
DOI10.1016/j.jchromb.2020.122051
英文摘要Destruction of assembly structures has been identified as a major cause for activity loss of virus and virus-like particles during their chromatographic process. A deep insight into the denaturation process at the solid-liquid interfaces is important for rational design of purification. In this study, in-situ differential scanning calorimetry (DSC) was employed to study the dissociation process of inactivated foot-and-mouth disease virus (FMDV) during ion exchange chromatography (IEC) at different levels of pH. The intact FMDV known as 146S and the dissociation products were quantified by high performance size exclusion chromatography (HPSEC) and the thermo-stability of 146S on-column was monitored in-situ by DSC. Serious dissociation was found at pH 7.0 and pH 8.0, leading to low 146S recoveries of 12.3% and 43.7%, respectively. The elution profiles from IEC and HPSEC combined with the thermal transition temperatures of 146S dissociation (T-m1) from DSC suggested two denaturation mechanisms that the 146S dissociation occurred on-column after adsorption at pH 7.0 and during elution step at pH 8.0. By appending different excipients including sucrose, the improvement of 146S recovery and reduced dissociation was found highly correlated to increment of 146S stability on-column detected by DSC. The highest recovery of 99.9% and the highest T-m1 of 54.49 degrees C were obtained at pH 9.0 with 20% (w/v) sucrose. According to chromatographic behaviors and T-m1, three different dissociation processes in IEC were discussed. The study provides a perspective to understand the denaturation process of assemblies during chromatography, and also supplies a strategy to improve assembly recovery.
WOS关键词DIFFERENTIAL SCANNING CALORIMETRY ; SIZE-EXCLUSION HPLC ; QUALITY-CONTROL ; PARTICLES ; PURIFICATION ; VACCINE ; ADSORPTION ; STABILITY ; ANTIGEN
资助项目National Natural Sciences Foundation of China[21808226] ; National Natural Sciences Foundation of China[21821005] ; National Natural Sciences Foundation of China[31970872]
WOS研究方向Biochemistry & Molecular Biology ; Chemistry
语种英语
WOS记录号WOS:000526729100009
出版者ELSEVIER
资助机构National Natural Sciences Foundation of China
源URL[http://ir.ipe.ac.cn/handle/122111/40034]  
专题中国科学院过程工程研究所
通讯作者Zhang, Songping; Su, Zhiguo
作者单位1.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.China Inst Vet Drug Control, Beijing 100081, Peoples R China
推荐引用方式
GB/T 7714
Yang, Yanli,Song, Yanmin,Lin, Xuan,et al. Mechanism of bio-macromolecule denaturation on solid-liquid surface of ion-exchange chromatographic media - A case study for inactivated foot-and-mouth disease virus[J]. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,2020,1142:10.
APA Yang, Yanli.,Song, Yanmin.,Lin, Xuan.,Li, Shuai.,Li, Zhengjun.,...&Su, Zhiguo.(2020).Mechanism of bio-macromolecule denaturation on solid-liquid surface of ion-exchange chromatographic media - A case study for inactivated foot-and-mouth disease virus.JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES,1142,10.
MLA Yang, Yanli,et al."Mechanism of bio-macromolecule denaturation on solid-liquid surface of ion-exchange chromatographic media - A case study for inactivated foot-and-mouth disease virus".JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES 1142(2020):10.

入库方式: OAI收割

来源:过程工程研究所

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