Oligomers ofβ2- and ofβ3-Homoproline: What are the Secondary Structures ofβ-Peptides Lacking H-Bonds?

To study the role of H-bonds in stabilizing β-peptidic secondary structures, we have synthesized β-oligopeptides (up to the octadecamer 12) consisting of β2- and β3-homoproline, i.e., β-peptides lacking amide protons. The enantiomer purity of the building block β2-homoproline (nipecotic acid, 4) was determined by HPLC analysis of the N-(2,4-dinitrophenyl) derivative 5 on a Chiralcel-OD column (cf. Fig. 2). The CD spectra of the all-(S)-β2- and all-(S)-β3-HPro-containing β-peptides display novel and intensive CD patterns which may be indicative of a secondary structure (cf. Fig. 3). It is noteworthy that a distinct CD pattern was observed with the β3-HPro derivatives containing as few as three residues (7a). The crystal structure of a N-deprotected β3-HPro-tripeptide 7c is presented (cf. Figs. 4 and 5), and a model for the structure of β-peptides consisting of β3-HPro is discussed (cf. Figs. 6 and 7).