Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12779/5457
Title: Solution structures of cyclosporin a and its complex with dysprosium(III) in SDS micelles: NMR and molecular dynamics studies
Authors: Bernardi, F
D'Amelio, N
Gaggelli, Elena 
Molteni, E
Valensin, Gianni 
Issue Date: 2008
Project: None 
Journal: JOURNAL OF PHYSICAL CHEMISTRY. B, CONDENSED MATTER, MATERIALS, SURFACES, INTERFACES & BIOPHYSICAL
Abstract: 
Cyclosporin A (CsA) is a cyclic naturally occurring peptide used to prevent graft rejection in organ transplantations. Its immunosuppressive activity is due to the formation of a complex with cyclophilin A (Cyp), in which the cis 9MeLeu−10MeLeu amide bond of CsA assumes a trans conformation. The mechanism of the conformational inversion has not been delineated, but it has been postulated that metal ions binding induces a conformational change that enables CsA to bind Cyp. In this work, we solved the structures of CsA in sodium dodecyl sulfate (SDS) micelles (which enhance its solubility and mimic the hydrophobic environment clinically used for drug delivery) and its complex with Dy(III) ion, whose coordination chemistry is frequently used to reproduce the effect of Ca(II). The paramagnetic properties of Dy(III) allowed us to build up a structure using proton relaxation enhancements, which remains stable in a MD simulation in the micelle environment.
Description: 
37772
URI: http://hdl.handle.net/20.500.12779/5457
ISSN: 1520-6106
DOI: 10.1021/jp076837z
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