title: Molecular characteristics of cyclophilin-cyclosporine interaction.
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.
authors.affiliation: Institut de Biologie Moléculaire et Cellulaire du CNRS, Strasbourg, France.
authors.forename: V F
authors.initials: VF
authors.lastname: Quesniaux
authors.forename: M H
authors.initials: MH
authors.lastname: Schreier
authors.forename: R M
authors.initials: RM
authors.lastname: Wenger
authors.forename: P C
authors.initials: PC
authors.lastname: Hiestand
authors.forename: M W
authors.initials: MW
authors.lastname: Harding
authors.forename: M H
authors.initials: MH
authors.lastname: Van Regenmortel
mesh_terms: D002147:Calmodulin / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D003524:Cyclosporins / Q000378:metabolism* / Q000494:pharmacology; D007165:Immunosuppression Therapy; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D019696:Peptidylprolyl Isomerase; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D002147:Calmodulin; D002352:Carrier Proteins; D003524:Cyclosporins; D019696:Peptidylprolyl Isomerase