2019
DOI: 10.1080/19420862.2019.1632114
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Binding symmetry and surface flexibility mediate antibody self-association

Abstract: Solution stability is an important factor in the optimization of engineered biotherapeutic candidates such as monoclonal antibodies because of its possible effects on manufacturability, pharmacology, efficacy and safety. A detailed atomic understanding of the mechanisms governing self-association of natively folded protein monomers is required to devise predictive tools to guide screening and re-engineering along the drug development pipeline. We investigated pairs of affinity-matured full-size antibodies and … Show more

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Cited by 11 publications
(19 citation statements)
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“…There are a lot of studies on interrelationships of protein flexibility, aggregation, and chemical stability. [244][245][246] Therefore, the method development for modeling protein flexibility is another important area in computeraided antibody design.…”
Section: Perspectivesmentioning
confidence: 99%
“…There are a lot of studies on interrelationships of protein flexibility, aggregation, and chemical stability. [244][245][246] Therefore, the method development for modeling protein flexibility is another important area in computeraided antibody design.…”
Section: Perspectivesmentioning
confidence: 99%
“…Previously, binding by ITC and BIAcore has been evaluated for a self-interacting antibody system [ 56 ], but no affinities were obtained. Only recently, self-binding affinities for strong self-interacting antibodies or antibody binding fragments have been measured using AUC and ITC methods [ 21 ]. Similar to the results obtained by Schrag and coworkers for Fab variants, our obtained binding affinities for Fab and/or mAb interactions were in the low μM range.…”
Section: Discussionmentioning
confidence: 99%
“…A resulting increase in viscosity may be exponential, making process filtration and pumping operations difficult and infeasible, and in the drug product form, handling, injectability, and potentially even stability may be negatively impacted [ 3 , 19 , 20 ]. This behavior is a major negative developability attribute that is difficult to predict from sequence or structure and correct through molecular engineering and can halt further development and the selection of even the most promising large-molecule candidates [ 21 ].…”
Section: Introductionmentioning
confidence: 99%
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