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

Autor: Wall A; Department of Chemistry, UCL, 20 Gordon St, London, WC1H 0AJ, UK. j.r.baker@ucl.ac.uk v.chudasama@ucl.ac.uk., Nicholls K; Albumedix Ltd, Castle Court, 59 Castle Boulevard, Nottingham NG7 1FD, UK., Caspersen MB; Albumedix Ltd, Castle Court, 59 Castle Boulevard, Nottingham NG7 1FD, UK., Skrivergaard S; Interdisciplinary Nanoscience Center (iNANO), Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, Denmark., Howard KA; Interdisciplinary Nanoscience Center (iNANO), Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, Denmark., Karu K; Department of Chemistry, UCL, 20 Gordon St, London, WC1H 0AJ, UK. j.r.baker@ucl.ac.uk v.chudasama@ucl.ac.uk., Chudasama V; Department of Chemistry, UCL, 20 Gordon St, London, WC1H 0AJ, UK. j.r.baker@ucl.ac.uk v.chudasama@ucl.ac.uk and Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal., Baker JR; Department of Chemistry, UCL, 20 Gordon St, London, WC1H 0AJ, UK. j.r.baker@ucl.ac.uk v.chudasama@ucl.ac.uk.
Jazyk: angličtina
Zdroj: Organic & biomolecular chemistry [Org Biomol Chem] 2019 Aug 28; Vol. 17 (34), pp. 7870-7873.
DOI: 10.1039/c9ob00721k
Abstrakt: 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.
Databáze: MEDLINE