کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8513725 | 1556499 | 2017 | 22 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Mapping the Binding Interface in a Noncovalent Size Variant of a Monoclonal Antibody Using Native Mass Spectrometry, Hydrogen-Deuterium Exchange Mass Spectrometry, and Computational Analysis
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Variants of monoclonal antibody containing an extra light chain have been reported in protein products. Due to potential impact on potency and immunogenicity, it is important to understand the formation mechanism of such variants so that appropriate control strategies can be implemented to assure product quality. In a model monoclonal antibody, we observed a size variant with an extra light chain noncovalently associated with the monomer (later named as “1.2mer”). The interaction between monomer and the extra light chain was characterized by native spray and hydrogen-deuterium exchange mass spectrometry techniques. The goal is to understand the nature of the noncovalent interaction, to map out the interaction interface and regions of potential conformational distortions. In addition, computational modeling was used to aid in binding site identification. The combined results identify the interaction interface to be located in the heavy chain region 38-57 and in the extra light chain region 30-50. To the best of our knowledge, this study is the first to characterize noncovalent interaction of a size variant comprising an antibody monomer and an extra light chain. Structural knowledge generated in this research work is invaluable for process development and construct design of antibody-based biopharmaceuticals.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 106, Issue 11, November 2017, Pages 3222-3229
Journal: Journal of Pharmaceutical Sciences - Volume 106, Issue 11, November 2017, Pages 3222-3229
نویسندگان
Yuetian Yan, Hui Wei, Sutjano Jusuf, Stanley R. Jr., Jie Chen, Guodong Chen, Richard T. Ludwig, Li Tao, Tapan K. Das,