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Structure of Rapamycin: An NMR and Molecular‐Dynamics Investigation
Author(s) -
Kessler Horst,
Haessner Rainer,
Schüler Wolfgang
Publication year - 1993
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19930760106
Subject(s) - heteronuclear molecule , chemistry , molecular dynamics , molecule , stereochemistry , coupling constant , carbon 13 nmr , two dimensional nuclear magnetic resonance spectroscopy , nuclear magnetic resonance spectroscopy , crystallography , computational chemistry , organic chemistry , physics , particle physics
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.