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Design and Synthesis of Conformationally Constrained Cyclophilin Inhibitors Showing a Cyclosporin‐A Phenotype in C. elegans
Author(s) -
Dunsmore Colin J.,
Malone Kirk J.,
Bailey Kevin R.,
Wear Martin A.,
Florance Hannah,
Shirran Sally,
Barran Perdita E.,
Page Antony P.,
Walkinshaw Malcolm D.,
Turner Nicholas J.
Publication year - 2011
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201000413
Subject(s) - cypa , cyclophilin a , cyclophilin , caenorhabditis elegans , chemistry , cis trans isomerases , small molecule , dipeptide , biochemistry , peptidylprolyl isomerase , stereochemistry , biology , enzyme , microbiology and biotechnology , isomerase , peptide , gene
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 .