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Genetic Encoding of a Non-Canonical Amino Acid for the Generation of Antibody-Drug Conjugates Through a Fast Bioorthogonal Reaction
Published on: September 14, 2018
Solution behavior of a novel biopharmaceutical drug candidate: a gonadotropin-toxin conjugate
Derrick S Katayama1, Mark Cornell Manning, Paul Jarosz
1Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
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 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.
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