Conformational changes in a Vernier zone region: Implications for antibody dual specificity

Proteins
Merve ArslanSibel Kalyoncu

Abstract

Understanding the determinants of antibody specificity is one of the challenging tasks in antibody development. Monospecific antibodies are still dominant in approved antibody therapeutics but there is a significant body of work to show that multispecific antibodies can increase the overall therapeutic effect. Dual-specific or "Two-in-One" antibodies can bind to two different antigens separately with the same antigen-binding site as opposed to bispecifics, which simultaneously bind to two different antigens through separate antigen-binding units. These nonstandard dual-specific antibodies were recently shown to be promising for new antibody-based therapeutics. Here, we physicochemically and structurally analyzed six different antibodies of which two are monospecific and four are dual-specific antibodies derived from monospecific templates to gain insight about dual-specificity determinants. These dual-specific antibodies can target both human epidermal growth factor receptor 2 and vascular endothelial growth factor at different binding affinities. We showed that a particular region of clustered Vernier zone residues might play key roles in gaining dual specificity. While there are minimal intramolecular interactions between a c...Continue Reading

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Citations

Mar 20, 2021·Frontiers in Immunology·Monica L Fernández-QuinteroKlaus R Liedl
Aug 28, 2021·Frontiers in Immunology·Monica L Fernández-QuinteroKlaus R Liedl

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