Folded conformation, cyclic pentamer, nanostructure, and PAD4 binding mode of YW3-56

The physical and chemical mechanisms of small molecules with pharmacological activity forming nanostructures are developing into a new field of nanomedicine. By using ROESY 2D NMR spectroscopy, tandem mass spectroscopy, transmission electron microscopy, and computer-assisted molecular modeling, this paper demonstrates the contribution of the folded conformation, the intra- and intermolecular π-π stacking, the intra- and intermolecular hydrogen bonds, and the receptor binding free energy of 6-dimethylaminonaph-2-yl-{N-S-[1- benzylcarba-moyl-4-(2-chloroacetamidobutyl)]-carboxamide (YW3-56) to the rapid formation of nanorings and the slow formation of nanocapsules. Thus we have developed a strategy that makes it possible to elucidate the physical and chemical mechanisms of bioactive small molecules forming nanostructures.