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Critical Reviews™ in Immunology
IF: 1.352 5-Year IF: 3.347 SJR: 0.657 SNIP: 0.55 CiteScore™: 2.19

ISSN Print: 1040-8401
ISSN Online: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v32.i6.30
pages 503-527

Thermodynamic Analysis to Assist in the Design of Recombinant Antibodies

Eric T. Mack
Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102
Paul J. Bracher
Beckman Institute, California Institute of Technology, Pasadena, CA 91125
Raquel Perez-Castillejos
Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102


This critical review examines the thermodynamics of binding of bivalent antibodies (IgG and IgE) to soluble ligands with two or more binding moieties joined covalently (multivalent ligands) and to surfaces functionalized with multiple identical ligands. Given the prevalence of antibodies in nature, the goal of this paper is to begin to understand what aspects of bivalent antibodies are important relative to their monovalent counterparts (Fab). We provide a brief introduction to the thermodynamic parameters of importance to bivalent binding, guidance as to which of these parameters are most useful for the comparison of disparate systems, and a re-examination of binding studies of bivalent antibodies from the literature. For all of the cases we examined, the intramolecular free energy of binding (ΔG°intra) was less favorable than the intermolecular free energy (ΔG°inter). The effective molarity (EM) and the ratio of the free energies of intramolecular and intermolecular binding (ΔG°intra/ΔG°inter) are tools to assess the particular contribution of intramolecular binding to the thermodynamics of bivalent association. The paper concludes with guidance to the reader on what to consider when designing experiments to study bivalent systems.