Solution behavior of a novel type 1 interferon, interferon-tau.
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 approximately 4 kcal/mole at room temperature. IFN-tau was found to remain monomeric upon increasing the protein concentration, even up to 60 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.
Katayama
Derrick S
DS
Center for Pharmaceutical Biotechnology, University of Colorado Health Sciences Center, Denver, Colorado, USA.
Nayar
Rajiv
R
Chou
Danny K
DK
Campos
Jackie
J
Cooper
Julianne
J
Vander Velde
David G
DG
Villarete
Lorelie
L
Liu
C P
CP
Cornell Manning
Mark
M
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D001483:Base Sequence; D002021:Buffers; D002417:Cattle; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral; D004355:Drug Stability; D019791:Guanidine / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007370:Interferon Type I / Q000737:chemistry* / Q000494:pharmacology; D008969:Molecular Sequence Data; D011257:Pregnancy Proteins / Q000737:chemistry* / Q000494:pharmacology; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012995:Solubility; D012996:Solutions; D012997:Solvents / Q000737:chemistry; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects
D000998:Antiviral Agents; D002021:Buffers; D007370:Interferon Type I; D011257:Pregnancy Proteins; D012996:Solutions; D012997:Solvents; C020947:interferon tau; D019791:Guanidine