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,) is used to evaluate the difference between the curves where the lower T, value corresponds to a higher aggregation propensity. The applicability of the method was demonstrated with human interleukin-1 receptor antagonist (IL-1 ra) 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. (c) 2008 Elsevier Inc. All rights reserved.