Studies on the binding sites of IgG2 monoclonal antibodies recognized by terpyridine-based affinity ligands

Chih-Pei Lin, Reinhard I Boysen, Eva M Campi, Kei Saito, Milton T W Hearn

Research output: Contribution to journalArticleResearchpeer-review

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. 

Original languageEnglish
Pages (from-to)334-342
Number of pages9
JournalJournal of Molecular Recognition
Volume29
Issue number7
DOIs
Publication statusPublished - 1 Jul 2016

Keywords

  • enthalpic and entropic effects
  • free energy changes
  • isothermal titration calorimetry
  • mixed mode adsorbents
  • molecular docking
  • monoclonal antibodies
  • protein–ligand interactions
  • terpyridinyl ligands

Cite this

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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. ",
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Studies on the binding sites of IgG2 monoclonal antibodies recognized by terpyridine-based affinity ligands. / Lin, Chih-Pei; Boysen, Reinhard I; Campi, Eva M; Saito, Kei; Hearn, Milton T W.

In: Journal of Molecular Recognition, Vol. 29, No. 7, 01.07.2016, p. 334-342.

Research output: Contribution to journalArticleResearchpeer-review

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