Optimised approach to albumin–drug conjugates using monobromomaleimide-C-2 linkers
Archie Wall, Karl Nicholls, Mikael B. Caspersen, Stig Skrivergaard, Kenneth A. Howard, Kersti Karu, Vijay Chudasama and James R. Baker
Org. Biomol. Chem., 2019, Advance Article
Abstract: Conjugation of therapeutics to human serum albumin (HSA) using bromomaleimides represents a promising platform for half-life extension. We show here that the Cys-34 crevice substantially reduces the rate of serum stabilising maleimide hydrolysis in these conjugates, necessitating reagent optimisation. This improved reagent design is applied to the construction of an HSA-paclitaxel conjugate, preventing drug loss during maleimide hydrolysis.