To understand the processes associated with small synthetic ligands binding large protein surfaces, NMR spectroscopy was used to examine the conformational changes in doxorubicin and lavendustin A upon binding to tetanus toxin. C13 T1 measurements suggested that to a first approximation, the conformational behavior of doxorubicin in solution appears to be a composite of a rigid aromatic ring system, ring librations for its cyclohexane and carbohydrate rings, and segmental motions for the pendant C(O)CH2OH group. trNOESY experiments indicated that both ligands adopt rigid conformations when bound to tetanus toxin and each binds a different site on the toxin surface.
