Simple Method Provides Resolution of Albumin, Lipoprotein, Free Fraction, and Chylomicron To Enhance the Utility of Protein Binding Assays

Medicinal chemists have been encouraged in recent years to embrace high speed protein binding assays. These methods employ dialysis membranes in 96-well format or spin filters. Membrane-based methods do not separate lipoprotein binding from albumin binding and introduce interference despite membrane...

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Veröffentlicht in:Journal of medicinal chemistry 2015-02, Vol.58 (3), p.1420-1425
Hauptverfasser: Brockman, Adam H, Oller, Haley R, Moreau, Benoît, Kriksciukaite, Kristina, Bilodeau, Mark T
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container_end_page 1425
container_issue 3
container_start_page 1420
container_title Journal of medicinal chemistry
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creator Brockman, Adam H
Oller, Haley R
Moreau, Benoît
Kriksciukaite, Kristina
Bilodeau, Mark T
description Medicinal chemists have been encouraged in recent years to embrace high speed protein binding assays. These methods employ dialysis membranes in 96-well format or spin filters. Membrane-based methods do not separate lipoprotein binding from albumin binding and introduce interference despite membrane binding controls. Ultracentrifugation methods, in contrast, do not introduce interference if density gradients can be avoided and they resolve lipoprotein from albumin. A new generation of compact, fast ultracentrifuges facilitates the rapid and fully informative separation of plasma into albumin, albumin/fatty acid complex, lipoprotein, protein-free, and chylomicron fractions with no need of salt or sugar density gradients. We present a simple and fast ultracentrifuge method here for two platinum compounds and a taxane that otherwise bound irreversibly to dialysis membranes and which exhibited distinctive lipoprotein binding behaviors. This new generation of ultracentrifugation methods underscores a need to further discuss protein binding assessments as they relate to medicinal chemistry efforts.
doi_str_mv 10.1021/jm501748h
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source MEDLINE; American Chemical Society Journals
subjects Albumins - chemistry
Bridged-Ring Compounds - chemistry
Chemistry, Pharmaceutical
Dialysis
Lipoproteins - chemistry
Molecular Structure
Organoplatinum Compounds - chemistry
Protein Binding
Taxoids - chemistry
Ultracentrifugation
title Simple Method Provides Resolution of Albumin, Lipoprotein, Free Fraction, and Chylomicron To Enhance the Utility of Protein Binding Assays
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