Photo-oxidation of IgG1 and Model Peptides: Detection and Analysis of Triply Oxidized His and Trp Side Chain Cleavage Products
| Autor: | Li Yi, Christian Schöneich, Jessica Bane, Y. John Wang, Alavattam Sreedhara, Olivier Mozziconacci |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Light Pharmaceutical Science Peptide Mass spectrometry Photochemistry Cleavage (embryo) 030226 pharmacology & pharmacy Mass Spectrometry 03 medical and health sciences Residue (chemistry) 0302 clinical medicine Photosensitivity Side chain Histidine Pharmacology (medical) Chromatography High Pressure Liquid Pharmacology chemistry.chemical_classification Alanine Photosensitizing Agents Chemistry Organic Chemistry Tryptophan 030104 developmental biology Immunoglobulin G Molecular Medicine Peptides Oxidation-Reduction Biotechnology |
| Zdroj: | Pharmaceutical Research. 34:229-242 |
| ISSN: | 1573-904X 0724-8741 |
| Popis: | Triply oxidized histidine in an IgG1 monoclonal antibody was noticed when exposed to ICH light conditions. In order to understand the role of light source, irradiation wavelengths and primary sequence, specifically those of a nearby tryptophan, we synthesized and exposed several peptides to ICH light conditions and analyzed the products using LC-MS analysis. Protein and peptide samples were photo-irradiated under ICH conditions as well as with monochromatic light at λ = 254 nm and analyzed using either LTQ Orbitrap or a LTQ-FT ion cyclotron resonance mass spectrometer respectively. A triply oxidized His residue was detected along with a second doubly oxidized His residue in an IgG1. Both of these oxidized His residues are located near Trp residues. In order to investigate the role of Trp photosensitization in His oxidation we synthesized model peptides and Ala mutants. Peptides exposed to ICH light stress conditions revealed a small percent of triply oxidized His in the Trp-containing peptide sequences but not in their corresponding Ala mutants. The differences in product formation under different photo-irradiation conditions underline the importance of light source, irradiation wavelengths and primary sequence in the photosensitivity of proteins. |
| Databáze: | OpenAIRE |
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