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.

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