Imidazolidinone-Tethered α-Hydrazidopeptides – Synthesis and Conformational Investigation

Nα-acylated β2,3-3-azapeptides, or α-hydrazidopeptides, of different lengths were synthesized starting from a conformationally restricted imidazolidinone-tethered monomer. The preferential conformations of the oligomers were investigated by NMR and CD spectroscopy, supported by computational analysis. The experimental data clearly confirmed the tendency of these α-hydrazidopeptides to fold into a zig-zag (Z8) 8-helix conformation, whose stability is length-dependent, stabilized by the C=O(i)···H-N(i+2) and N(i)···H-N(i+1) intramolecular H-bonding pattern, as well as by non-standard C=O···H-C hydrogen bonds