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Updated: Jul 3, 2026

Structure-Guided Design and Development of Novel Cyclophilin A Inhibitors and Ganoderiol-F Derivatives: An In-Silico Approach
Published on: June 23, 2026
Dynamic combinatorial self-assembly of cyclophilin hCyp-18 ligands through oxorhenium coordination
Cécile Clavaud1, Julien Le Gal, Robert Thai
1CEA, Institut de Biologie et de Technologie de Saclay (iBiTecS), Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), Bâtiment 152, 91191 Gif-sur-Yvette, France.
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.
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