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Engineering Ph-Dependent Antibody Interactions Through Linked Protonation Events In Interdomain Interfaces, Hyeyoung Eom Jan 2020

Engineering Ph-Dependent Antibody Interactions Through Linked Protonation Events In Interdomain Interfaces, Hyeyoung Eom

Graduate Research Theses & Dissertations

Engineered antibodies are frequently used in life science applications, such as therapeutics and clinical diagnostics. These customized antibodies typically possess enhanced binding affinity and/or specificity, yet these interactions are only one-way binding events that cannot be easily controlled without extreme changes in conditions, such as pH, denaturant, and/or temperature that likely irreversible damage the antibody and antigen. Here, we explore the design of proton-linked binding events in the context of both antibody/hapten (i.e., a low molecular weight ligand target) and antibody/antigen complexes. Specifically, this work looks to overcome the challenges of engineering pH-dependent small ligand/protein interactions, as well as develop …