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Protein formulations containing polysorbates : are metal chelators needed at all?
ID
Brovč, Ema Valentina
(
Avtor
),
ID
Pajk, Stane
(
Avtor
),
ID
Šink, Roman
(
Avtor
),
ID
Mravljak, Janez
(
Avtor
)
PDF - Predstavitvena datoteka,
prenos
(4,63 MB)
MD5: B6DD1DAE7F4589CDAD1A86A5FE909AC8
URL - Izvorni URL, za dostop obiščite
https://www.mdpi.com/2076-3921/9/5/441
Galerija slik
Izvleček
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
Število ogledov:
1214
Število prenosov:
116
Metapodatki:
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Objavi na:
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
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