Structure of Rapamycin: An NMR and Molecular-Dynamics Investigation

The highly active immunosuppressive antibiotic rapamycin is a specific inhibitor of a signal transduction pathway that results in exocytosis and transcription. We report the results of the homo‐ and heteronuclear NMR experiments of rapamycin in DMSO leading to a complete assignment of the 1H‐ and 13C‐NMR signals. With exception of one CH2 group, all diastereotopic assignments could be achieved using heteronuclear long‐range coupling constants. Restrained molecular‐dynamics simulation in the same solvent as the NMR experiments led to a well defined conformation of the rapamycin molecule in solution. Differences between the solution and crystal structures are discussed.