Photo-induced site-specific oxidative fragmentation of IgG1 mediated by iron(III)-containing histidine buffer: Mechanistic studies and excipient effects

Zhang, Yilue; Ballesteros, M.; Schöneich, Christian

doi:10.1016/j.ejpb.2023.07.011

Cited by 3 publications

(3 citation statements)

References 57 publications

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“…Earlier, we reported on a ferric iron-mediated site-specific oxidative cleavage of the NISTmAb heavy chain at THR259, rationalized by a tentative binding pocket for Fe(III) provided by amino acid residues ASP252, THR259, and GLU261. , Therefore, MD simulation was utilized to investigate whether Fe(III) interacts with these residues. Figure presents the distances of Fe(III) to oxygen atoms in the side chains of THR259, ASP252, and GLU261 where the side chain hydroxyl group of THR is protonated, i.e., the THR259 is in the THR259 (0) state.…”

Section: Resultsmentioning

confidence: 99%

“…Earlier, we reported on a ferric iron-mediated site-specific oxidative cleavage of the NISTmAb heavy chain at THR259, rationalized by a tentative binding pocket for Fe(III) provided by amino acid residues ASP252, THR259, and GLU261. 14,15 Therefore, MD simulation was utilized to investigate whether Fe(III) ASP252. However, in the absence of Fe(III), due to the repulsive interaction between the carboxylate groups of ASP252 and GLU261, the Fe(III)-forced short distances between the two residues are unlikely to be maintained.…”

Section: Distance Of Fe(iii) To Oxygen Atoms On the Sidementioning

confidence: 99%

“…14 Recently, we reported on a site-specific oxidative cleavage of an IgG1 (NISTmAb), mediated by Fe(III)-containing histidine buffer when exposed to visible light. 14,15 This cleavage specifically targeted residue THR259 in the Fc domain. Our observations were rationalized by LMCT within a Fe(III)binding pocket close to the cleavage site, 14 supported by inhibition of IgG1 fragmentation by the addition of EDTA.…”

Section: Introductionmentioning

confidence: 99%

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Molecular Dynamics Simulation of an Iron(III) Binding Site on the Fc Domain of IgG1 Relevant for Visible Light-Induced Protein Fragmentation

Lou,

Zhang,

Kuczera

et al. 2023

Mol. Pharmaceutics

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Molecular dynamics simulations were employed to investigate the interaction between Fe(III) and an iron-binding site composed of THR259, ASP252, and GLU261 on the Fc domain of an IgG1. The goal was to provide microscopic mechanistic information for the photochemical, iron-dependent site-specific oxidative fragmentation of IgG1 at THR259 reported in our previous paper. The distance between Fe(III) and residues of interest as well as the binding pocket size was examined for both protonated and deprotonated THR259. The Fe(III) binding free energy (ΔG) was estimated by using an umbrella sampling approach. The pK a shift of the THR259 hydroxyl group caused by the presence of nearby Fe(III) was estimated based on a thermodynamic cycle. The simulation results show that Fe(III) resides inside the proposed binding pocket and profoundly changes the pocket configuration. The ΔG values indicate that the pocket possesses a strong binding affinity for Fe(III). Furthermore, Fe(III) profoundly lowers the pK a value of the THR259 hydroxyl group by 5.4 pK a units.

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Section: Resultsmentioning

confidence: 99%

“…Earlier, we reported on a ferric iron-mediated site-specific oxidative cleavage of the NISTmAb heavy chain at THR259, rationalized by a tentative binding pocket for Fe(III) provided by amino acid residues ASP252, THR259, and GLU261. 14,15 Therefore, MD simulation was utilized to investigate whether Fe(III) ASP252. However, in the absence of Fe(III), due to the repulsive interaction between the carboxylate groups of ASP252 and GLU261, the Fe(III)-forced short distances between the two residues are unlikely to be maintained.…”

Section: Distance Of Fe(iii) To Oxygen Atoms On the Sidementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Molecular Dynamics Simulation of an Iron(III) Binding Site on the Fc Domain of IgG1 Relevant for Visible Light-Induced Protein Fragmentation

Lou,

Zhang,

Kuczera

et al. 2023

Mol. Pharmaceutics

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Visible light triggers the formation of reactive oxygen species in monoclonal antibody formulations

Hipper,

Diederichs,

Kaiser

et al. 2024

International Journal of Pharmaceutics

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Removal of amoxicillin employing Fenton-type process using delaminated clay and layered double hydroxides impregnated with Fe or Cu as catalysts

Lugo,

Diaz,

Contreras

et al. 2024

Preprint

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The presence of antibiotics in the environment has raised concerns due to their potential negative effects on ecosystems. Conventional water treatment methods are ineffective at removing antibiotics. This study aims to investigate the efficiency of Fenton-like processes catalyzed by delaminated clay and layered double hydroxides impregnated with Fe or Cu for the degradation of amoxicillin. The catalysts were obtained by synthesizing delaminated clay and layered double hydroxides and subsequently impregnating them with Fe or Cu. The characterization of catalysts involved X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray fluorescence (XRF), N2 adsorption-desorption, and X-ray photoelectron spectroscopy (XPS). Catalytic activity was assessed by varying the concentration of hydrogen peroxide, the initial concentration of amoxicillin, and the amount of catalyst. The determination of byproducts was done by high-performance liquid chromatography (HPLC) with a quadrupole time-of-flight mass spectrometer (QqTof). The study found that layered double hydroxides impregnated with Fe or Cu were able to remove 100% of amoxicillin in just 20 min. The study identified 16 byproducts, indicating a degradation process. Under all of the studied conditions, the copper catalysts showed the highest percentage of amoxicillin removal.

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Photo-induced site-specific oxidative fragmentation of IgG1 mediated by iron(III)-containing histidine buffer: Mechanistic studies and excipient effects

Cited by 3 publications

References 57 publications

Molecular Dynamics Simulation of an Iron(III) Binding Site on the Fc Domain of IgG1 Relevant for Visible Light-Induced Protein Fragmentation

Molecular Dynamics Simulation of an Iron(III) Binding Site on the Fc Domain of IgG1 Relevant for Visible Light-Induced Protein Fragmentation

Visible light triggers the formation of reactive oxygen species in monoclonal antibody formulations

Removal of amoxicillin employing Fenton-type process using delaminated clay and layered double hydroxides impregnated with Fe or Cu as catalysts

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