Hierarchical Self-Assembly of Aminopyrazole Peptides into Nanorosettes in Water

Self-association of aminopyrazole peptide hybrid 1 leads to stacked nanorosettes. This
remarkable, well-ordered structure obeys the laws of nucleic acid self-assembly. In a strictly hierarchical
process, formation of aminopyrazole “base” triplets via a hydrogen bond network is accompanied by
π-stacking with a second rosette and final dimerization of two double rosettes to a four-layer superstructure,
stabilized by a six-fold half-crown alkylammonium lock. The final complex is soluble in organic as well as
in aqueous solution. It was characterized in the solid state by X-ray crystallography, in water by NMR
spectroscopy, and in silico by quantum chemical shift calculation. All these methods provide strong evidence
for the same hexameric complex geometry. Its structural features bear striking silimarity to nucleic acid
architectures and their peptidic counterparts, especially alanyl-PNA. The whole self-assembly process is
highly solvent- and temperature-dependent and occurs with a high degree of cooperativityno intermediates
are observed. Formation and dissociation of the nanorosette, however, are kinetically slow. The limitation
to a hexameric aggregate can be explained by six sterically demanding valine residues, whose replacement
by alanines may result in formation of infinite fibers.