Estimation of protein aggregation propensity with a melting point apparatus.
A method for studying protein aggregation with an automated melting point apparatus is described. The method employs thermal ramping and can generate a series of protein aggregation curves. The midpoint aggregation curve-associated temperature (T(a)) is used to evaluate the difference between the curves where the lower T(a) value corresponds to a higher aggregation propensity. The applicability of the method was demonstrated with human interleukin-1 receptor antagonist (IL-1ra) as a protein aggregation model. The method could be employed for rapid evaluation of various factors such as mutations, buffers, and excipients influencing protein aggregation propensity under the thermal stress.
Raibekas
Andrei A
AA
Department of Pharmaceutics, Amgen, Thousand Oaks, CA 91320, USA. andreir@amgen.com
D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000737:chemistry*; D009391:Nephelometry and Turbidimetry; D011506:Proteins / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D013053:Spectrophotometry / Q000379:methods; D013696:Temperature
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D011506:Proteins; D011994:Recombinant Proteins