Abstract
Cyclophilin A (CypA) is a member of the immunophilin family of proteins and receptor for the immunosuppressant drug cyclosporin A (CsA). Here we describe the design and synthesis of a new class of small-molecule inhibitors for CypA that are based upon a dimedone template. Electrospray mass spectrometry is utilised as an initial screen to quantify the protein affinity of the ligands. Active inhibitors and fluorescently labelled derivatives are then used as chemical probes for investigating the biological role of cyclophilins in the nematode Caenorhabditis elegans.
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Caenorhabditis elegans / drug effects*
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Caenorhabditis elegans / metabolism
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Caenorhabditis elegans Proteins / antagonists & inhibitors*
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Caenorhabditis elegans Proteins / metabolism
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Cyclophilin A / antagonists & inhibitors*
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Cyclophilin A / metabolism
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Cyclosporine
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Drug Design
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology*
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Ligands
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Models, Molecular
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Protein Binding
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Small Molecule Libraries / chemistry*
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Small Molecule Libraries / pharmacology*
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Spectrometry, Mass, Electrospray Ionization
Substances
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Caenorhabditis elegans Proteins
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Enzyme Inhibitors
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Ligands
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Small Molecule Libraries
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Cyclosporine
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Cyclophilin A