Sequence-Dependence of secondary structure formation: Conformational studies of host-guest peptides in α-helix and β-structure supporting media

A newly designed host–guest approach is introduced as a experimental tool to explore the relationship between the sequence of peptides and their secondary structure. From the CD spectra of the host–guest peptides studied, a tentative scale for the α‐helix potential in 2,2,2‐trifluorethanol of guest amino acids is delineated. The conformational preferences are also examined in β‐structure supporting media (solid state, CH2Cl2, CH3OH, H2O) using ir‐absorption and CD techniques. Scales for the β‐forming tendency of guest amino acid residues in the different media are delineated. It is shown that the preferred conformation of the host–guest peptides is a function of the medium, the chain length, and the protecting groups. Given the fact that conformational effects are important in peptide synthesis, the tentative scales may serve as a guideline to predict secondary structures of side‐chain‐protected or ‐deprotected peptides in a given solvent, complementing the well‐known empirical conformational prediction parameters.