CD Spectra in Methanol ofβ-Oligopeptides Consisting ofβ-Amino Acids with Functionalized Side Chains, with Alternating Configuration, and with Geminal Backbone Substituents - Fingerprints of New Secondary Structures?

Abstract

β-Hexa-, β-hepta-, and β-nonapeptides, 1 – 6, which carry functionalized side chains (CO2R, CO, (CH2)4NH, CH2−CH=CH2) consisting of β3-amino-acid residues of alternating configuration, or which carry geminal substituents in the 2- or 3-positions of all residues, have been synthesized (Schemes 1 – 3), and their CD spectra in MeOH are reported (Figs. 2 – 6). Strong Cotton effects (Θ>105) are indicative of the presence of chiral secondary structures. It is suggested by simple modelling (Fig. 1) that the new β-peptides should not be able to fold to the familiar 314-helical structures. Still, three of them (3, 4, and 5) give rise to CD spectra matching those of β-peptides that are known to be present as (M)- or (P)-314-helices in MeOH solution. While possible folding motifs (Figs. 3,b, and 7) of the new β-peptides have been identified in crystal structures, an interpretation of the CD spectra has to be postponed until NMR solution structures become available. A list of all β-peptides giving rise to CD spectra with a minimum near 215 nm is included (Table).