Dynamic Combinatorial Self‐Assembly of Cyclophilin hCyp‐18 Ligands through Oxorhenium Coordination

Abstract

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 peptidyl-prolyl isomerase-was investigated. Increasing glutathione (GSH) concentrations were used to dissociate [ARe(V)OB] 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 % (CC(50)) 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 micromolar to submicromolar range.