Structure of Rapamycin: An NMR and Molecular‐Dynamics Investigation

Abstract

Abstract 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 1 H‐ and 13 C‐NMR signals. With exception of one CH 2 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.