title: Structure refinement of cyclosporin A in chloroform by using RDCs measured in a stretched PDMS-gel.
abstract: New developments concerning alignment media for apolar solvents like chloroform make it possible to measure anisotropic parameters such as residual dipolar couplings (RDCs) at relatively low concentrations and natural isotopic abundance. As RDCs provide structural restraints with respect to an external coordinate system, long-range structural arrangements of the time-averaged structure can be determined with high precision. The method is demonstrated on the well-studied cyclo-undecapeptide Cyclosporin A (CsA), for which crystal and conventionally derived NMR structures are available. Neither crystal nor NMR structure are consistent with heteronuclear D(CH) RDCs measured in a stretched poly(dimethylsiloxane) gel, and refinement by using the anisotropic parameter results in a highly defined structure with a slightly changed backbone conformation. The applied methods and interpretation of the structural model are discussed.
authors.affiliation: Department Chemie, Lehrstuhl für Organische Chemie II, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Klages
authors.forename: Cajetan
authors.initials: C
authors.lastname: Neubauer
authors.forename: Murray
authors.initials: M
authors.lastname: Coles
authors.forename: Horst
authors.initials: H
authors.lastname: Kessler
authors.forename: Burkhard
authors.initials: B
authors.lastname: Luy
mesh_terms: D002725:Chloroform; D018360:Crystallography, X-Ray; D016572:Cyclosporine / Q000737:chemistry*; D005782:Gels / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation
chemical_list: D005782:Gels; D002725:Chloroform; D016572:Cyclosporine