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Biotechnology and Applied Biochemistry (2003) 38, (151–156) (Printed in Great Britain)

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L-Tyrosine prevents aggregation of therapeutic proteins by g-irradiation

Emma Assemand*, Monique Lacroix† and Mircea-Alexandru Mateescu*¹

*Department of Chemistry and Biochemistry, Université du Québec à Montréal, CP 8888, Succ. A, Montréal, Québec H3C 3P8, Canada, and †INRS-Institut Armand Frappier, 531 Blvd. des Prairies, Laval, Québec H7V 1B7, Canada

Key words: caeruloplasmin, conformational alteration, haemoglobin, protein processing, tyrosine.

Abbreviations used: CP, caeruloplasmin; Hb, haemoglobin.

¹To whom correspondence should be addressed (e-mail mateescu.m-alexandru@uqam.ca).

The present paper describes a protective role of L-tyrosine against aggregation of caeruloplasmin and haemoglobin therapeutic proteins during their sterilization by g-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 g-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 g-irradiation treatment.

Received 28 February 2003/19 May 2003; accepted 29 May 2003

Published as Immediate Publication 29 May 2003, DOI 10.1042/BA20030038

© 2003 Portland Press Ltd