Solution Behavior of a Novel Biopharmaceutical Drug Candidate: A Gonadotropin-Toxin Conjugate

ABSTRACT

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°C, the conjugate retains a significant amount of secondary and tertiary structure. Heating for 1 h at 60°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.

KEYWORDS:

• Solution structure and stability
• peptide and protein conjugate