Mapping site-specific changes that affect stability of the N-terminal domain of calmodulin.

Biophysical tools have been invaluable in formulating therapeutic proteins. These tools characterize protein stability rapidly in a variety of solution conditions, but in general, the techniques lack the ability to discern site-specific information to probe how solution environment acts to stabilize or destabilize the protein. NMR spectroscopy can provide site-specific information about subtle structural changes of a protein under different conditions, enabling one to assess the mechanism of protein stabilization.

Effects of stabilizers on the destabilization of proteins upon adsorption to aluminum salt adjuvants.

Excipients for protein-based vaccines are currently identified by evaluating the stability of the protein in solution. In most cases, however, the protein is adsorbed to the surface of an aluminum salt adjuvant in the final vaccine formulation. Previous studies showed that model protein antigens may be structurally altered and less thermally stable upon adsorption to aluminum salt adjuvants [Jones LS, Peek LJ, Power J, Markham A, Yazzie B, Middaugh CR, 2005, J Biol Chem 280:13406-13414].

Thermal stability of adenovirus type 2 as a function of pH.

Although several recent studies have focused on the characterization and formulation of adenovirus type 5, similar efforts focusing on adenovirus type 2 (Ad2) have been lacking. To this end, multiple biophysical techniques were employed to investigate the thermal stability of Ad2 as a function of pH. Highly cooperative thermally induced changes in capsid conformation were detected near 45 and 65 degrees C under neutral conditions.