Conformational Analysis of the cis‐ and trans‐Isomers of FK506 by NMR and Molecular Dynamics

Dale F. Mierke, Peter Schmieder, Peter Karuso, Horst Kessler*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)


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 HH 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.

Original languageEnglish
Pages (from-to)1027-1047
Number of pages21
JournalHelvetica Chimica Acta
Issue number5
Publication statusPublished - 1991


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