Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2488081 | Journal of Pharmaceutical Sciences | 2005 | 13 Pages |
Abstract
Interferon-tau (IFN-tau) is a novel cytokine that appears during fetal development of mammals. It is currently being investigated for treatment of viral infections and autoimmune diseases. In order to develop a commercial product, a stable formulation will need to be identified. In this study, the solution behavior of IFN-tau was studied using a variety of biophysical methods. The overall structure of IFN-tau is well defined, with the polypeptide chain folding into a four-helix bundle structure, much like other type 1 interferons. However, its solution behavior has not been characterized. The globular structure has a free energy of unfolding of â¼4 kcal/mole at room temperature. IFN-tau was found to remain monomeric upon increasing the protein concentration, even up to 60Â mg/mL. The overall structure of IFN-tau is maintained across a pH range of 2-8, but is significantly altered in the presence of nonaqueous solvents. However, IFN-tau appears to refold efficiently when diluted into an aqueous medium from a nonaqueous solution. This behavior allows the protein to be formulated in low water content formulations suitable for use in capsules. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association.
Related Topics
Health Sciences
Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Derrick.S. Katayama, Rajiv Nayar, Danny K. Chou, Jackie Campos, Julianne Cooper, David G. Vander Velde, Lorelie Villarete, C.P. Liu, Mark Cornell Manning,