Solution Structures of Cyclosporin A and Its Complex with Dysprosium(III) in SDS Micelles: NMR and Molecular Dynamics Studies

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• 作者：Francesca Bernardi ; Nicola D'Amelio ; Elena Gaggelli ; Elena Molteni ; Gianni Valensin
• 刊名：Journal of Physical Chemistry B
• 出版年：2008
• 出版时间：January 24, 2008
• 年：2008
• 卷：112
• 期：3
• 页码：828 - 835
• 全文大小：664K
• 年卷期：v.112,no.3(January 24, 2008)
• ISSN：1520-5207

文摘

Cyclosporin A (CsA) is a cyclic naturally occurring peptide used to prevent graft rejection in organtransplantations. 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 mechanismof the conformational inversion has not been delineated, but it has been postulated that metal ions bindinginduces a conformational change that enables CsA to bind Cyp. In this work, we solved the structures of CsAin sodium dodecyl sulfate (SDS) micelles (which enhance its solubility and mimic the hydrophobic environmentclinically used for drug delivery) and its complex with Dy(III) ion, whose coordination chemistry is frequentlyused to reproduce the effect of Ca(II). The paramagnetic properties of Dy(III) allowed us to build up a structureusing proton relaxation enhancements, which remains stable in a MD simulation in the micelle environment.