Protein-drug conjugates are a rapidly expanding family of therapeutics that hold significant potential to ameliorate off-target toxic effects commonly observed in patients undergoing chemotherapy. In this context, the protein acts as a nanoscale delivery vector that alters the biodistribution of the drug upon administration by restricting its unhindered distribution in vivo. Researchers at TWU are exploring the use of cobalt coordination chemistry in the synthesis of doxorubicin-albumin conjugates. Previous work has shown that cobalt can be used to crosslink amine-containing molecules in a reversible reaction that only utilizes the lone pair of electrons on nitrogen to form a dative bond with cobalt. Doxorubicin was chosen for initial studies because it contains a primary amine that could be crosslinked with lysine residues on a protein to form a protein-drug conjugate. The effect of each reactant concentration (dox, cobalt, albumin, and base) on the synthesis of dox-albumin conjugates was investigated. Bound dox was determined by dialyzing each sample (3,500 MWCO) in PBS and monitoring the bulk phase by HPLC. Samples were further characterized by DLS and mass spectrometry where protein aggregation was observed to occur under some conditions. Optimized reaction conditions for synthesizing conjugates with 1-10 dox molecules per protein will be discussed.

Synthesis of doxorubicin-albumin conjugates via cobalt coordination chemistry: Effect of reaction conditions on drug loading

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.