Synthesis of a Hybrid Peptide with Both α- and β-Amino Acid Residues: Toward a New β-Sheet Nucleator

A hybrid peptide was synthesized from a pentameric β-peptide (5) with two strands of a dimeric natural peptide (l-Val-l-Leu) attached to β-amino acid residues 1 and 4. The trifluoroacetate (7) of the hybrid peptide 6 was readily soluble in a variety of organic solvents indicating an ordered structure. All nine amide NH protons are separated between 7.4 and 8.8 ppm in CDCl3 containing 5% DMSO(-d6). The downfield shift of the amide NH protons is an indication that hydrogen bonds are present. The CD spectrum of 7 in methanol is consistent with a β-sheet structure.