Protein formulations containing polysorbates : are metal chelators needed at all?

Brovč, Ema Valentina (avtor), Pajk, Stane (avtor), Šink, Roman (avtor), Mravljak, Janez (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: proteins, oxidation, Fenton reaction, free radicals, chelating agents, polysorbates
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2020
• Št. strani: 13 str.
• Številčenje: Vol. 9, iss. 5, art. 441
• PID: 20.500.12556/RUL-133676
• UDK: 615.4:54:547.466
• ISSN pri članku: 2076-3921
• DOI: 10.3390/antiox9050441
• COBISS.SI-ID: 16128003
• Datum objave v RUL: 08.12.2021

Gradivo je del revije

• Naslov: Antioxidants
• Skrajšan naslov: Antioxidants
• Založnik: MDPI
• ISSN: 2076-3921
• COBISS.SI-ID: 522976025

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 20.05.2020

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: farmacevtska kemija, aminokisline, beljakovine, oksidativnost, prosti radikali, polisorbati