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- Title
Conformational Analysis of the cis- and trans-Isomers of FK506 by NMR and Molecular Dynamics.
- Authors
Mierke, Dale F.; Schmieder, Peter; Karuso, Peter; Kessler, Horst
- Abstract
The potent immunosuppressant drug FK506 ( 2) has been examined by 1H- and 13C-NMR spectroscopy and NOE-restrained molecular dynamics to elucidate the conformation in solution. A combination of two- and three-dimensional NMR techniques was used to completely assign the 1H- and 13C-NMR chemical shifts of the two configurational isomers resulting from the cis- trans isomerization about the single amide bond. Hetero- and homonuclear coupling constants were measured to assign the diastereotopic methylene protons at C(16), C(18), and C(23). Intramolecular HH distances were defined from NOESY spectra recorded at −30° in CDCl3 and used as constraints in molecular-dynamics simulations. The conformational preferences of 2 in solution are discussed in light of the constitutional features recently proposed to be necessary for binding and activity.
- Publication
Helvetica Chimica Acta, 1991, Vol 74, Issue 5, p1027
- ISSN
0018-019X
- Publication type
Article
- DOI
10.1002/hlca.19910740513