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Competing aggregation pathways for monoclonal antibodies
Author(s) -
Wu Haixia,
Kroe-Barrett Rachel,
Singh Sanjaya,
Robinson Anne S.,
Roberts Christopher J.
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.01.051
Subject(s) - monoclonal antibody , chemistry , protein aggregation , antibody , kinetics , biophysics , agrégation , hot spot (computer programming) , biochemistry , biology , immunology , physics , platelet , quantum mechanics , computer science , operating system
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.