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

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

Chembiochem

CEA, Institut de Biologie et de Technologie de Saclay (iBiTecS), Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), Bâtiment 152, 91191 Gif-sur-Yvette, France.

Published: July 2008

AI Article Synopsis

Article 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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http://dx.doi.org/10.1002/cbic.200800187DOI Listing

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