Enhancement of antibody selectivity via bicyclic complex formation

Jared F. Stefanick, Tanyel Kiziltepe, Michael W. Handlogten, Nathan J. Alves, Basar Bilgicer

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

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 (K d = 0.14 μM) compared to the monovalent mimotope (K d = 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 potential method to enhance therapeutic antibody selectivity for diseased cells.

Original languageEnglish (US)
Pages (from-to)598-602
Number of pages5
JournalJournal of Physical Chemistry Letters
Volume3
Issue number5
DOIs
StatePublished - Mar 1 2012
Externally publishedYes

ASJC Scopus subject areas

  • Materials Science(all)
  • Physical and Theoretical Chemistry

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