A 500-MHZ PROTON NMR-STUDY OF THE CONFORMATION OF ADRIAMYCIN

The conformation of adriamycin has been investigated by proton NMR spectroscopy at 500 MHz in D2O and DMSO. Two-dimensional phase-sensitive COSY spectra are recorded to obtain three-bond and long-range coupling constants and hence torsional angles. Interproton distances are estimated from 2D phase-sensitive NOESY spectra using r(1H-2H)= 2.36 Angstrom as internal reference. Pairs of protons correlated by spin-spin coupling give NOE cross peaks with interproton distances < 3.3 Angstrom. Besides these contacts, several other NOE contacts are observed between protons within ring A and within the daunosamine sugar, and between ring A and the daunosamine sugar. It is also observed that protons 7H, 8axH and 8eqH of ring A are close to protons 1'H, 3'H, 4'H, 5'H and 5'CH3 of the daunosamine sugar with distances lying in the range 2.40-3.90 Angstrom. The 6OH proton is in the proximity of the 1'H and 3'NH3+ protons of the daunosamine sugar. The NOE contacts 5'H-8axH, 5'H-8eqH, 5'CH3-8axH, 5'CH3-8eqH and 1'H-7H are found to have a strong influence on the solution conformation of the adriamycin molecule determined on the basis of coupling constants and interproton distances.