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L-tyrosine prevents aggregation of therapeutic proteins by gamma-irradiation
Emma Assemand1, Monique Lacroix, Mircea-Alexandru Mateescu
1Department of Chemistry and Biochemistry, Université du Québec à Montréal, CP 8888, Succ. A, Montréal, Québec H3C 3P8, Canada.
Abstract:
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.
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