title: Studies on the binding sites of IgG2 monoclonal antibodies recognized by terpyridine-based affinity ligands.
abstract: This investigation has examined the origin of the molecular recognition associated with the interaction of monoclonal IgG2's with terpyridine-based ligands immobilized onto agarose-derived chromatographic adsorbents. Isothermal titration calorimetric (ITC) methods have been employed to acquire thermodynamic data associated with the IgG2-ligand binding. These ITC investigations have documented that different enthalpic and entropic processes are involved depending on the nature of the chemical substituents in the core structure of the terpyridinyl moiety. In addition, molecular docking studies have been carried out with IgG2 structures with the objective to identify possible ligand binding sites and key interacting amino acid residues. These molecular docking experiments with the different terpyridine-based ligands have shown that all of the examined ligands can potentially undergo favorable interactions with a site located within the Fab region of the IgG2. However, another favorable binding site was also identified from the docking poses to exist within the Fc region of the IgG2 for some, but not all, of the ligands studied. These investigations have provided a basis to elucidate the unique binding properties and chromatographic behaviors shown by several substituted terpyridine ligands in their interaction with IgGs of different isotype. Copyright © 2016 John Wiley & Sons, Ltd.
authors: School of Chemistry, Monash University, Melbourne, VIC, 3800, Australia.
authors: Chih-Pei
authors: CP
authors: Lin
authors: School of Chemistry, Monash University, Melbourne, VIC, 3800, Australia.
authors: Reinhard I
authors: RI
authors: Boysen
authors: School of Chemistry, Monash University, Melbourne, VIC, 3800, Australia.
authors: Eva M
authors: EM
authors: Campi
authors: School of Chemistry, Monash University, Melbourne, VIC, 3800, Australia.
authors: Kei
authors: K
authors: Saito
authors: School of Chemistry, Monash University, Melbourne, VIC, 3800, Australia.
authors: Milton T W
authors: MT
authors: Hearn
mesh_terms: D020816:Amino Acid Motifs; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D002151:Calorimetry; D007074:Immunoglobulin G / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D011485:Protein Binding; D013816:Thermodynamics
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D008024:Ligands
keywords: enthalpic and entropic effects; free energy changes; isothermal titration calorimetry; mixed mode adsorbents; molecular docking; monoclonal antibodies; protein-ligand interactions; terpyridinyl ligands