Vibrational circular-dichroism spectroscopy of homologous cyclic peptides designed to fold into β helices of opposite chirality.

Cyclic β-helical peptides have been developed as model structured biomolecules for examining peptide adsorption and conformation on surfaces. As a key prerequisite to circular-dichroism (CD) analysis of these model peptides on surfaces, their conformations and the corresponding vibrational spectra in the 1400-1800 cm⁻¹ range were analyzed by vibrational circular-dichroism (VCD) spectroscopy in solution. The two model peptides ("β Leu and β Val") were examined in chloroform, where they each fold into a homogeneous well-defined antiparallel double-stranded β-helical species, as determined previously by NMR and electronic CD spectroscopy. Because the β-helical conformations of β Leu and β Val are well characterized, the VCD spectra of these peptides can be unambiguously correlated with their structures. In addition, these two β-helical peptides differ from one another in two key respects that make them uniquely advantageous for CD analysis--first, while their backbone conformations are topologically similar, β Leu and β Val form helices of opposite chiralities; second, the two peptides differ in their sequences, i.e., composition of the side chains attached to the backbone. The observed VCD spectra for β Leu and β Val are roughly mirror images of each other, indicating that the VCD features are dominated by the chirality and conformation of the peptide backbone rather than by the peptide sequence. Accordingly, spectra similarly characteristic of peptide secondary structure can be expected for peptides designed to be structural analogs of β Leu and β Val while incorporating a variety of side chains for studies of surface adsorption from organic and aqueous solvents.