FTIR markers of methionine oxidation for early detection of oxidized protein therapeutics

The biological activity of therapeutic proteins is strongly dependent on the stability of their folded state, which can easily be compromised by degradation. Oxidation is one of the most common causes of degradation and is typically associated with impairment of the native protein structure. Methion...

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Veröffentlicht in:European biophysics journal 2011-03, Vol.40 (3), p.339-345
Hauptverfasser: Ravi, Jascindra, Hills, Anna E., Cerasoli, Eleonora, Rakowska, Paulina D., Ryadnov, Maxim G.
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container_end_page 345
container_issue 3
container_start_page 339
container_title European biophysics journal
container_volume 40
creator Ravi, Jascindra
Hills, Anna E.
Cerasoli, Eleonora
Rakowska, Paulina D.
Ryadnov, Maxim G.
description The biological activity of therapeutic proteins is strongly dependent on the stability of their folded state, which can easily be compromised by degradation. Oxidation is one of the most common causes of degradation and is typically associated with impairment of the native protein structure. Methionine residues stand out as particularly susceptible to oxidation by reactive oxygen intermediates even under mild conditions. Consequently, methionine oxidation has profound effects on protein activity up to the point of adverse biological responses. Of immediate importance therefore is finding affordable approaches for rapid detection of methionine oxidation before any substantial structural changes can ensue. Herein we report that vibrational bands at 1,044 and 1,113 cm −1 in the mid-infrared region can serve as characteristic markers of methionine oxidation in oxidatively stressed protein therapeutics, monoclonal antibodies (IgG1 and its antigen-binding fragment). Such Fourier-transform infrared (FTIR) markers underpin rapid detection assays and hold particular promise for correlation of methionine oxidation with protein structure and function.
doi_str_mv 10.1007/s00249-010-0656-1
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Oxidation is one of the most common causes of degradation and is typically associated with impairment of the native protein structure. Methionine residues stand out as particularly susceptible to oxidation by reactive oxygen intermediates even under mild conditions. Consequently, methionine oxidation has profound effects on protein activity up to the point of adverse biological responses. Of immediate importance therefore is finding affordable approaches for rapid detection of methionine oxidation before any substantial structural changes can ensue. Herein we report that vibrational bands at 1,044 and 1,113 cm −1 in the mid-infrared region can serve as characteristic markers of methionine oxidation in oxidatively stressed protein therapeutics, monoclonal antibodies (IgG1 and its antigen-binding fragment). 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subjects Biochemistry
Biodegradation
Biological and Medical Physics
Biomarkers - analysis
Biomarkers - chemistry
Biomedical and Life Sciences
Biophysics
Biophysics Letter
Cell Biology
Circular Dichroism - methods
Fourier transforms
Immunoglobulin Fab Fragments - analysis
Immunoglobulin Fab Fragments - chemistry
Immunoglobulin Fab Fragments - therapeutic use
Immunoglobulin Fc Fragments - analysis
Immunoglobulin Fc Fragments - chemistry
Immunoglobulin Fc Fragments - therapeutic use
Immunoglobulin G - analysis
Immunoglobulin G - chemistry
Immunoglobulin G - therapeutic use
Life Sciences
Membrane Biology
Methionine - analogs & derivatives
Methionine - analysis
Methionine - chemistry
Nanotechnology
Neurobiology
Oxidation
Oxidation-Reduction
Oxidative Stress
Proteins
Quantitative Structure-Activity Relationship
Spectrometry, Fluorescence
Spectroscopy, Fourier Transform Infrared
Spectrum analysis
title FTIR markers of methionine oxidation for early detection of oxidized protein therapeutics
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