Open AccessActinomycin D, 1 H NMR studies on intramolecular interactions and on the planarity of the chromophore
Author(s) -
JURETSCHKE Hans Paul,
LAPIDOT Aviva
Publication year - 1984
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1984.tb08418.x
Subject(s) - chromophore , intramolecular force , chemistry , molecule , amide , chloroform , resonance (particle physics) , hydrogen bond , planarity testing , nuclear magnetic resonance spectroscopy , amino acid , crystallography , proton nmr , stereochemistry , ring (chemistry) , photochemistry , organic chemistry , biochemistry , physics , particle physics
The conformation of actinomycin D in acetone and chloroform solution at different temperatures has been studied by 1 H NMR spectroscopy. At lower temperature the resonances due to the two chromophoric amino protons were observed. These signals exhibit very different resonance positions indicating a severely hindered rotation of the 2‐amino group and the presence of a hydrogen‐bond connecting the 2‐amino and the 1‐carbonyl groups. In 1 H NMR spectra of partially 15 N‐enriched actinomycin D, the 1 J N‐H coupling constants at the 2‐amino group were determined and a strong sp 2 character for the 2‐amino nitrogen was deduced. The strong amide character of the 2‐amino group is caused by mesomerism involving the 1‐carbonyl group. The amino proton signals are sensitive indicators for differences in the spatial relationship of the diverse parts of the actinomycin molecule. At lower temperatures a simultaneous and selective broadening of the α ring threonine and valine amide proton signals as well as of the 2‐amino group resonance was observed, indicating the presence of one dynamic process in the molecule which slows down upon temperature reduction. A swinging motion of the N(10) nitrogen through the chromophore plane would explain this observation. The interpretation of these results requires the presence of a non‐planar chromophoric system in the actinomycin molecule in acetone and chloroform solution. The possible implications of this non‐planarity for the intercalation process and for the biological activity of the drug are discussed.