Oxidation of free L-histidine by tert-Butylhydroperoxide.

Purpose: L-histidine, a commonly used buffer for protein formulations, has the potential to oxidize and form multiple byproducts. Previous studies were performed using metal catalyzed oxidation with Fe(2+) or Cu(2+). We re-examined the oxidation of L-histidine under conditions more appropriate to protein formulations.

Anion binding and controlled aggregation of human interleukin-1 receptor antagonist.

Highly concentrated human recombinant interleukin-1 receptor antagonist (IL-1ra) aggregates at elevated temperature without perturbation in its secondary structure. The protein aggregation can be suppressed depending on the buffer ionic strength and the type of anion present in the sample solution. Phosphate is an approximately 4-fold weaker suppressant than either citrate or pyrophosphate on the basis of the measured protein aggregation rates.