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

Archie Hall; Karl  Nicholls; Mikael B.  Caspersen; Stig Skrivergaard; Ken Howard; Kersti Karu; Vijay Chudasama; James R. Baker

doi:10.1039/C9OB00721K

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

Archie Hall, Karl Nicholls , Mikael B. Caspersen , Stig Skrivergaard, Ken Howard, Kersti Karu, Vijay Chudasama, James R. Baker

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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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.

Original language	English
Journal	Organic & Biomolecular Chemistry
Volume	17
Issue	34
Pages (from-to)	7870-7873
Number of pages	4
ISSN	1477-0520
DOIs	https://doi.org/10.1039/C9OB00721K
Publication status	Published - 2019

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10.1039/C9OB00721KLicence: CC BY

Optimised approach to albumin-drug conjugates using monobromomaleimide-C-2 linkersFinal published version, 1.78 MBLicence: CC BY

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title = "Optimised approach to albumin-drug conjugates using monobromomaleimide-C-2 linkers",

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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Optimised approach to albumin-drug conjugates using monobromomaleimide-C-2 linkers. / Hall, Archie; Nicholls , Karl ; Caspersen , Mikael B. et al.
In: Organic & Biomolecular Chemistry, Vol. 17, No. 34, 2019, p. 7870-7873.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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 -

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

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