Thermodynamic analysis to assist in the design of recombinant antibodies

Document Type

Article

Publication Date

12-1-2012

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. © 2012 by Begell House, Inc.

Identifier

84873740214 (Scopus)

Publication Title

Critical Reviews in Immunology

External Full Text Location

https://doi.org/10.1615/CritRevImmunol.v32.i6.30

ISSN

10408401

PubMed ID

23428226

First Page

503

Last Page

527

Issue

6

Volume

32

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