Design and Synthesis of Conformationally Constrained Cyclophilin Inhibitors Showing a Cyclosporin-A Phenotype in C. elegans

Dunsmore, C.J., Malone, K.J., Bailey, K.R., Wear, M.A., Florance, H., Shirran, S., Barran, P.E., Page, A.P. , Walkinshaw, M.D. and Turner, N.J. (2011) Design and Synthesis of Conformationally Constrained Cyclophilin Inhibitors Showing a Cyclosporin-A Phenotype in C. elegans. ChemBioChem, 12(5), pp. 802-810. (doi: 10.1002/cbic.201000413) (PMID:21337480)

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Publisher's URL: http://dx.doi.org/10.1002/cbic.201000413

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Page, Professor Tony
Authors: Dunsmore, C.J., Malone, K.J., Bailey, K.R., Wear, M.A., Florance, H., Shirran, S., Barran, P.E., Page, A.P., Walkinshaw, M.D., and Turner, N.J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:ChemBioChem
ISSN:1439-4227

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
407991Chemical mapping of the PPIase interactome in C elegans - development of a systems biology toolboxAntony PageBiotechnology and Biological Sciences Research Council (BBSRC)BB/D006201/1Infection Immunity and Inflammation Life Sciences