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Enhancement Of Antibody Selectivity Via Bicyclic Complex Formation

J. F. Stefanick, T. Kiziltepe, Michael W Handlogten, N. Alves, B. Bilgicer
Published 2012 · Chemistry

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This study describes a strategy where antibody selectivity for high antigen-density surfaces is enhanced by forming a thermodynamically stable bicyclic complex. The bicyclic complex was formed via multivalent interactions of the antibody with a synthetic trivalent mimotope at a 3:2 molar ratio. Complex formation was analyzed using dynamic light scattering and analytical ultracentrifugation, showing a hydrodynamic radius of ∼22 nm and a calculated molecular weight of 397 kDa, depicting a trimeric complex formation. The complex has high thermodynamic stability and results in a 10-fold higher binding affinity for the trivalent mimotope (Kd = 0.14 μM) compared to the monovalent mimotope (Kd = 1.4 μM). As bicyclic complexes, the antibodies showed ∼18% binding of the monomeric form to low antigen-density surfaces. At high antigen-density, antibody binding was equal whether delivered as a complex or a monomer. These results establish bicyclic complex selectivity for high antigen-density surfaces and suggest a po...
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