title: Thermodynamic analysis to assist in the design of recombinant antibodies.
abstract: 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.
authors: Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA.
authors: Eric T
authors: ET
authors: Mack
authors: Paul J
authors: PJ
authors: Bracher
authors: Raquel
authors: R
authors: Perez-Castillejos
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000737:chemistry / Q000378:metabolism*; D015195:Drug Design; D006801:Humans; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D018033:Antibodies, Bispecific; D011994:Recombinant Proteins