FTIR markers of methionine oxidation for early detection of oxidized protein therapeutics
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. 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.
Early detection, Fourier-transform infrared, IR marker bands, Methionine oxidation, Protein therapeutics (IgG1 and antigen-binding fragment)
339-345
Ravi, Jascindra
d0c93c4d-3a20-4b47-83de-588adc502509
Hills, Anna E.
938675fe-081c-44f0-91eb-3d43b3b9d72d
Cerasoli, Eleonora
18ce2ec4-cab6-4367-8c8c-b6ba12d8ab55
Rakowska, Paulina D.
73bf2145-e2fa-46ee-9ad9-f74c80d5a369
Ryadnov, Maxim G.
0621e854-f160-40c6-ab8d-1afbf48089fd
13 January 2011
Ravi, Jascindra
d0c93c4d-3a20-4b47-83de-588adc502509
Hills, Anna E.
938675fe-081c-44f0-91eb-3d43b3b9d72d
Cerasoli, Eleonora
18ce2ec4-cab6-4367-8c8c-b6ba12d8ab55
Rakowska, Paulina D.
73bf2145-e2fa-46ee-9ad9-f74c80d5a369
Ryadnov, Maxim G.
0621e854-f160-40c6-ab8d-1afbf48089fd
Ravi, Jascindra, Hills, Anna E., Cerasoli, Eleonora, Rakowska, Paulina D. and Ryadnov, Maxim G.
(2011)
FTIR markers of methionine oxidation for early detection of oxidized protein therapeutics.
European Biophysics Journal, 40 (3), .
(doi:10.1007/s00249-010-0656-1).
Abstract
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.
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Accepted/In Press date: 30 November 2010
Published date: 13 January 2011
Additional Information:
Funding Information:
Acknowledgments We thank Technology Strategy Board and NMO of the UK for financial support. We also thank Prof. George Tranter for critical discussions and GSK and UCB for providing mAb and fAb for the study.
Keywords:
Early detection, Fourier-transform infrared, IR marker bands, Methionine oxidation, Protein therapeutics (IgG1 and antigen-binding fragment)
Identifiers
Local EPrints ID: 485937
URI: http://eprints.soton.ac.uk/id/eprint/485937
ISSN: 0175-7571
PURE UUID: aa195487-4edf-4309-9bfb-1ab335d859e4
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Date deposited: 04 Jan 2024 04:57
Last modified: 18 Mar 2024 03:59
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Contributors
Author:
Jascindra Ravi
Author:
Anna E. Hills
Author:
Eleonora Cerasoli
Author:
Maxim G. Ryadnov
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