L-tyrosine prevents aggregation of therapeutic proteins by gamma-irradiation.
The present paper describes a protective role of L-tyrosine against aggregation of caeruloplasmin and haemoglobin therapeutic proteins during their sterilization by gamma-irradiation in the aqueous phase. Irradiation of proteins, known to induce their degradation in the presence of oxygen, generates aggregation under oxygen-free conditions. It was found that L-tyrosine present during irradiation in deoxygenated media prevents protein aggregation even at high doses (10 kGy), as asserted by SDS/PAGE and high-performance size-exclusion chromatography. The protective role of L-tyrosine, allowing the gamma-irradiation treatment of therapeutic proteins in solution without conformational alteration, is probably exerted by scavenging oxygen radicals produced by irradiation-induced water radiolysis. It was also found that haemoglobin had a greater stability than caeruloplasmin under gamma-irradiation treatment.
Assemand
Emma
E
Department of Chemistry and Biochemistry, Université du Québec à Montréal, CP 8888, Succ. A, Montréal, Québec H3C 3P8, Canada.
Lacroix
Monique
M
Mateescu
Mircea-Alexandru
MA
D000818:Animals; D002417:Cattle; D002570:Ceruloplasmin / Q000378:metabolism / Q000528:radiation effects* / Q000627:therapeutic use; D002845:Chromatography; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005720:Gamma Rays; D006454:Hemoglobins / Q000378:metabolism / Q000528:radiation effects* / Q000627:therapeutic use; D012995:Solubility; D013242:Sterilization / Q000379:methods*; D014443:Tyrosine / Q000494:pharmacology* / Q000502:physiology
D006454:Hemoglobins; D014443:Tyrosine; D002570:Ceruloplasmin