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Protein formulations containing polysorbates [Elektronski vir] : are metal chelators needed at all?Brovč, Ema Valentina ...Proteins are prone to post-translational modifications at specific sites, which can affect their physicochemical properties, and consequently also their safety and efficacy. Sources of ... post-translational modifications include oxygen and reactive oxygen species. Additionally, catalytic amounts of Fe(II) or Cu(I) can promote increased activities of reactive oxygen species, and thus catalyse the production of particularly reactive hydroxyl radicals. When oxidative post-translational modifications are detected in the biopharmaceutical industry, it is common practice to add chelators to the formulation. However, the resultant complexes with metals can be even more damaging. Indeed, this is supported here using an ascorbate redox system assay and peptide mapping. Ethylenediaminetetraacetic acid (EDTA) addition strongly accelerated the formation of hydroxyl radicals in an iron-ascorbate system, while diethylenetriaminepentaacetic acid (DTPA) addition did not. When Fe(III) was substituted with Cu(II), EDTA addition almost stopped hydroxyl radical production, whereas DTPA addition showed continued production, but at a reduced rate. Further, EDTA accelerated metal-catalysed oxidation of proteins, and thus did not protect them from Fe-mediated oxidative damage. As every formulation is unique, justification for EDTA or DTPA addition should be based on experimental data and not common practice.Source: Antioxidants [Elektronski vir]. - ISSN 2076-3921 (Vol. 9, Iss. 5, 2020, str. 1-13)Type of material - e-article ; adult, seriousPublish date - 2020Language - englishCOBISS.SI-ID - 16128003
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https://www.mdpi.com/2076-3921/9/5/441/htmOdprt dostop
Repository of the University of Ljubljana – RUL
DOI
Author
Brovč, Ema Valentina |
Pajk, Stane, 1983- |
Šink, Roman |
Mravljak, Janez, 1978-
Topics
Farmacevtska kemija |
Aminokisline |
proteins |
oxidation |
Fenton reaction |
free radicals |
chelating agents |
polysorbates |
beljakovine |
oksidativnost |
prosti radikali |
polisorbati
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Brovč, Ema Valentina | 50716 |
Pajk, Stane, 1983- | 28861 |
Šink, Roman | 28862 |
Mravljak, Janez, 1978- | 23419 |
Source: Personal bibliographies
and: SICRIS
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