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Effect of benzyl alcohol on recombinant human interleukin-1 receptor antagonist structure and hydrogen–deuterium exchange

✍ Scribed by John R. Alford; Andrew C. Fowler; Deborah S. Wuttke; Bruce A. Kerwin; Ramil F. Latypov; John F. Carpenter; Theodore W. Randolph


Publisher
John Wiley and Sons
Year
2011
Tongue
English
Weight
505 KB
Volume
100
Category
Article
ISSN
0022-3549

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✦ Synopsis


Benzyl alcohol, a preservative commonly added to multidose therapeutic protein formulations, can accelerate aggregation of recombinant human interleukin-1 receptor antagonist (rhIL-1ra). To investigate the interactions between benzyl alcohol and rhIL-1ra, we used nuclear magnetic resonance to observe the effect of benzyl alcohol on the chemical shifts of amide resonances of rhIL-1ra and to measure hydrogen-deuterium exchange rates of individual rhIL-1ra residues. Addition of 0.9% benzyl alcohol caused significant chemical shifts of amide resonances for residues 90-97, suggesting that these solvent-exposed residues participate in the binding of benzyl alcohol. In contrast, little perturbation of exchange rates was observed in the presence of either sucrose or benzyl alcohol.


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