Competing aggregation pathways for monoclonal antibodies

被引：62
|
作者：
Wu, Haixia [1 ,2 ]
Kroe-Barrett, Rachel [2 ]
Singh, Sanjaya [2 ]
Robinson, Anne S. [3 ,4 ]
Roberts, Christopher J. [4 ]
机构：
[1] Univ Delaware, Dept Chem & Biochem, Newark, DE 19711 USA
[2] Boehringer Ingelheim Pharmaceut Inc, Dept Biotherapeut, Ridgefield, CT 06877 USA
[3] Tulane Univ, Dept Chem & Biomol Engn, New Orleans, LA 70118 USA
[4] Univ Delaware, Dept Chem & Biomol Engn, Newark, DE 19711 USA
来源：
FEBS LETTERS | 2014年 / 588卷 / 06期
关键词：
MAb; Aggregation; Hot-spot; DIFFERENTIAL SCANNING CALORIMETRY; COLONY-STIMULATING FACTOR; LUMRY-EYRING MODELS; PROTEIN SHELF-LIFE; MULTIDOMAIN PROTEIN; ALPHA-CHYMOTRYPSINOGEN; NONNATIVE AGGREGATION; IGG1; ANTIBODY; STABILITY; IMMUNOGLOBULIN;
D O I：
10.1016/j.febslet.2014.01.051
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Aggregation is mediated by local unfolding to allow aggregation "hot spot(s)'' to become solvent exposed and available to associate with a hot spot on another partially unfolded protein. Historically, the unfolding of either the crystallizable fragment (Fc) or the antigen binding fragment (Fab) regions of a given monoclonal antibody (MAb) has been implicated in aggregation, with differing results across different proteins. The present work focuses on separately quantifying the aggregation kinetics of isolated Fc, isolated Fab, and intact MAb as a function of pH under accelerated (high temperature) conditions. The results show that both Fab and Fc are aggregation prone and compete within the same MAb. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码：936 / 941
页数：6
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