Dynamic combinatorial self-assembly of cyclophilin hCyp-18 ligands through oxorhenium coordination

The dynamic combinatorial assembly of independent modules A and B through oxorhenium(V) coordination by a NS2 + S motif in the presence of cyclophilin hCyp-18-an important peptidylprolyl isomerase-was investigated. Increasing glutathione (GSH) concentrations were used to dissociate [A-(ReO)-O-v.B] complexes that displayed low affinity for hCyp-18. Conversely, coordinates that displayed submicromolar affinities for hCyp-18 were protected against thiol exchange and could be detected by LC-MS. Determination of the GSH concentration that decreased the extracted ionic current of the complex by 50% (CC50) enabled the selection of three oxorhenium coordinates that were shown to bind to the active site of hCyp-18 and to inhibit its peptidyl-prolyl isomerase activity in the micromolor to submicromolor range.