Molecular characteristics of cyclophilin-cyclosporine interaction.

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Quesniaux VF, Schreier MH, Wenger RM, Hiestand PC, Harding MW, Van Regenmortel MH

Molecular characteristics of cyclophilin-cyclosporine interaction.

Transplantation. 1988 Aug;46(2 Suppl):23S-28S. doi: 10.1097/00007890-198808001-00005.

PubMed ID

2970139 [ View in PubMed

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Abstract

The ability of cyclophilin to react with derivatives of cyclosporine (CsA) was studied. Cyclophilin was found to interact preferentially with CsA-residues 1, 2, 10 and 11, which, together with residue 3, are the residues known to contribute to the immunosuppressive activity of CsA. The recognition of different CsA-derivatives by cyclophilin was correlated with their immunosuppressive activity in vitro. All CsA-derivatives showing a significant activity did bind to cyclophilin, although some of the CsA-derivatives able to bind cyclophilin exhibited only low activities. The results suggest that binding to cyclophilin might be one requirement for immunosuppressive activity of CsA derivatives. When tested with CsA-derivatives showing various conformational changes, the binding of cyclophilin was strongly specific for the peptide-ring conformation of CsA. No binding of calmodulin to CsA could be detected in several formats of solid-phase enzyme- or radioimmunoassay, suggesting that, in contrast to cyclophilin, calmodulin does not possess sufficient affinity for CsA to bind to it when immobilized on the solid phase.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Cyclosporine	Peptidyl-prolyl cis-trans isomerase F, mitochondrial	Protein	Humans	Yes	Binder	Details