Optimised approach to albumin-drug conjugates using monobromomaleimide-C-2 linkers

TY - JOUR

T1 - Optimised approach to albumin-drug conjugates using monobromomaleimide-C-2 linkers

AU - Hall, Archie

AU - Nicholls , Karl

AU - Caspersen , Mikael B.

AU - Skrivergaard, Stig

AU - Howard, Ken

AU - Karu, Kersti

AU - Chudasama, Vijay

AU - Baker, James R.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

U2 - 10.1039/C9OB00721K

DO - 10.1039/C9OB00721K

M3 - Journal article

SN - 1477-0520

VL - 17

SP - 7870

EP - 7873

JO - Organic & Biomolecular Chemistry

JF - Organic & Biomolecular Chemistry

IS - 34

ER -