Solution behavior of a novel biopharmaceutical drug candidate: a gonadotropin-toxin conjugate.
There is little known about the solution structure and stability of peptide-protein conjugates, which comprise a new class of potential biopharmaceutical agents. This study describes the solution behavior of gonadotropins-releasing hormone (GnRH) chemically conjugated to pokeweed antiviral protein (PAP). The conjugate adopts a well-defined conformation across a pH range of 4 to 8. Even after heating to 80 degrees C, the conjugate retains a significant amount of secondary and tertiary structure. Heating for 1 h at 60 degrees C does lead to chemical damage, as determined by cation exchange chromatography. Using an experimental design approach, the optimal pH and salt concentration for limiting chemical damage was determined.
Katayama
Derrick S
DS
Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Cornell Manning
Mark
M
Jarosz
Paul
P
D015195:Drug Design; D004355:Drug Stability; D005615:Freezing; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage* / Q000737:chemistry; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D046912:Multiprotein Complexes; D009699:N-Glycosyl Hydrolases / Q000008:administration & dosage* / Q000737:chemistry; D010940:Plant Proteins / Q000008:administration & dosage* / Q000737:chemistry; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D054789:Ribosome Inactivating Proteins, Type 1; D012996:Solutions
D046912:Multiprotein Complexes; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D012996:Solutions; D007987:Gonadotropin-Releasing Hormone; D009699:N-Glycosyl Hydrolases; C024275:pokeweed antiviral protein