Enhancement of antibody selectivity via bicyclic complex formation

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

Research output: Contribution to journalArticle

10 Citations (Scopus)

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

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antibodies
Antibodies
antigens
Antigens
selectivity
augmentation
Dynamic light scattering
affinity
molecular weight
Thermodynamic stability
light scattering
Hydrodynamics
monomers
Monomers
Molecular weight
hydrodynamics
thermodynamics
radii
cells
interactions

ASJC Scopus subject areas

  • Materials Science(all)

Cite this

Enhancement of antibody selectivity via bicyclic complex formation. / Stefanick, Jared F.; Kiziltepe, Tanyel; Handlogten, Michael W.; Alves, Nathan; Bilgicer, Basar.

In: Journal of Physical Chemistry Letters, Vol. 3, No. 5, 01.03.2012, p. 598-602.

Research output: Contribution to journalArticle

Stefanick, JF, Kiziltepe, T, Handlogten, MW, Alves, N & Bilgicer, B 2012, 'Enhancement of antibody selectivity via bicyclic complex formation', Journal of Physical Chemistry Letters, vol. 3, no. 5, pp. 598-602. https://doi.org/10.1021/jz201682z
Stefanick, Jared F. ; Kiziltepe, Tanyel ; Handlogten, Michael W. ; Alves, Nathan ; Bilgicer, Basar. / Enhancement of antibody selectivity via bicyclic complex formation. In: Journal of Physical Chemistry Letters. 2012 ; Vol. 3, No. 5. pp. 598-602.
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