Purification of Human Immunoglobulin G with Bathophenanthroline–Zn<sup>2+</sup>, –Fe<sup>2+</sup>, or –Cu<sup>2+</sup> Complexes

Background/Objectives: Pharmaceutical companies are aware of the ongoing effort to satisfy the increasing global demand for therapeutic-grade monoclonal antibodies (mAbs), an especially difficult challenge for poor and developing countries. We present a simple, economical, single-step purification a...

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Main Authors: Thisara Jayawickrama Withanage, Ron Alcalay, Olga Krichevsky, Ellen Wachtel, Ohad Mazor, Guy Patchornik
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Antibodies
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Online Access:https://www.mdpi.com/2073-4468/14/2/40
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author Thisara Jayawickrama Withanage
Ron Alcalay
Olga Krichevsky
Ellen Wachtel
Ohad Mazor
Guy Patchornik
author_facet Thisara Jayawickrama Withanage
Ron Alcalay
Olga Krichevsky
Ellen Wachtel
Ohad Mazor
Guy Patchornik
author_sort Thisara Jayawickrama Withanage
collection DOAJ
description Background/Objectives: Pharmaceutical companies are aware of the ongoing effort to satisfy the increasing global demand for therapeutic-grade monoclonal antibodies (mAbs), an especially difficult challenge for poor and developing countries. We present a simple, economical, single-step purification approach at neutral pH for polyclonal human IgG (hIgG), which does not require any expensive ligands, chromatography columns, polymers, or membranes. Methods/Results: Instead, porous precipitates of commercial, recyclable aromatic [bathophenanthroline:cation] complexes were found to efficiently capture impurity proteins from CHO cells or <i>E. coli</i> lysate while maintaining the majority of the highly concentrated hIgG (5–15 mg/mL) in the supernatant. [(Batho)<sub>3</sub>:Zn<sup>2+</sup>] complexes were the most promising, resulting in hIgG with a purity of ≈95%, by SDS-PAGE. This purified hIgG is monomeric (by dynamic light scattering, DLS) and preserves the native secondary structure (by far UV circular dichroism spectroscopy, CD). The process yield is >90% (by densitometry) and is maintained after a 100-fold increase in the reaction volume, which required only proportional increases in reagents. Conclusions: Although Protein A chromatographic columns, the industry gold standard, have a limited binding capacity, are costly, and require familiarity with column maintenance, we are attempting, by our efforts, to help to produce a more efficient, simple, and economical purification platform.
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spelling doaj-art-b422c8df4ccd477e91ec7a0df8d94b302025-08-20T03:27:26ZengMDPI AGAntibodies2073-44682025-05-011424010.3390/antib14020040Purification of Human Immunoglobulin G with Bathophenanthroline–Zn<sup>2+</sup>, –Fe<sup>2+</sup>, or –Cu<sup>2+</sup> ComplexesThisara Jayawickrama Withanage0Ron Alcalay1Olga Krichevsky2Ellen Wachtel3Ohad Mazor4Guy Patchornik5Department of Chemical Sciences, Ariel University, Ariel 70400, IsraelIsrael Institute for Biological Research, Ness Ziona 7410001, IsraelDepartment of Chemical Sciences, Ariel University, Ariel 70400, IsraelFaculty of Chemistry, Weizmann Institute of Science, Rehovot 76100, IsraelIsrael Institute for Biological Research, Ness Ziona 7410001, IsraelDepartment of Chemical Sciences, Ariel University, Ariel 70400, IsraelBackground/Objectives: Pharmaceutical companies are aware of the ongoing effort to satisfy the increasing global demand for therapeutic-grade monoclonal antibodies (mAbs), an especially difficult challenge for poor and developing countries. We present a simple, economical, single-step purification approach at neutral pH for polyclonal human IgG (hIgG), which does not require any expensive ligands, chromatography columns, polymers, or membranes. Methods/Results: Instead, porous precipitates of commercial, recyclable aromatic [bathophenanthroline:cation] complexes were found to efficiently capture impurity proteins from CHO cells or <i>E. coli</i> lysate while maintaining the majority of the highly concentrated hIgG (5–15 mg/mL) in the supernatant. [(Batho)<sub>3</sub>:Zn<sup>2+</sup>] complexes were the most promising, resulting in hIgG with a purity of ≈95%, by SDS-PAGE. This purified hIgG is monomeric (by dynamic light scattering, DLS) and preserves the native secondary structure (by far UV circular dichroism spectroscopy, CD). The process yield is >90% (by densitometry) and is maintained after a 100-fold increase in the reaction volume, which required only proportional increases in reagents. Conclusions: Although Protein A chromatographic columns, the industry gold standard, have a limited binding capacity, are costly, and require familiarity with column maintenance, we are attempting, by our efforts, to help to produce a more efficient, simple, and economical purification platform.https://www.mdpi.com/2073-4468/14/2/40antibody purificationIgGnon-chromatographicligand-freeProtein A
spellingShingle Thisara Jayawickrama Withanage
Ron Alcalay
Olga Krichevsky
Ellen Wachtel
Ohad Mazor
Guy Patchornik
Purification of Human Immunoglobulin G with Bathophenanthroline–Zn<sup>2+</sup>, –Fe<sup>2+</sup>, or –Cu<sup>2+</sup> Complexes
Antibodies
antibody purification
IgG
non-chromatographic
ligand-free
Protein A
title Purification of Human Immunoglobulin G with Bathophenanthroline–Zn<sup>2+</sup>, –Fe<sup>2+</sup>, or –Cu<sup>2+</sup> Complexes
title_full Purification of Human Immunoglobulin G with Bathophenanthroline–Zn<sup>2+</sup>, –Fe<sup>2+</sup>, or –Cu<sup>2+</sup> Complexes
title_fullStr Purification of Human Immunoglobulin G with Bathophenanthroline–Zn<sup>2+</sup>, –Fe<sup>2+</sup>, or –Cu<sup>2+</sup> Complexes
title_full_unstemmed Purification of Human Immunoglobulin G with Bathophenanthroline–Zn<sup>2+</sup>, –Fe<sup>2+</sup>, or –Cu<sup>2+</sup> Complexes
title_short Purification of Human Immunoglobulin G with Bathophenanthroline–Zn<sup>2+</sup>, –Fe<sup>2+</sup>, or –Cu<sup>2+</sup> Complexes
title_sort purification of human immunoglobulin g with bathophenanthroline zn sup 2 sup fe sup 2 sup or cu sup 2 sup complexes
topic antibody purification
IgG
non-chromatographic
ligand-free
Protein A
url https://www.mdpi.com/2073-4468/14/2/40
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