STEREOCHEMICAL STUDIES ON CYCLIC PEPTIDES .3. CONFORMATIONAL ANALYSIS OF CYCLOTETRAPEPTIDES

A conformational study of cyclotetraalanyl has been made on the basis of contact criteria as well as from potential energy considerations. Using planar peptide units, it is possible to have ring closure only when the value of τ at the linking Ca atoms is less than 100°, which is too small. However, when non-planarity of the peptide unit is introduced, a stable conformation is possible with l-alanyl residues for a four-fold symmetric structure, with conformational parameters (ω, φ{symbol}, ψ) equal to (-12°, 90°, 125°). These are fairly close to the corresponding values for the α-helical conformation of poly-l-alanine. This supports the observation of Balasubramanian and Wetlaufer that this cyclic peptide bears close resemblance to the α-helix in its ORD characteristics. It is possible to have a similar structure with d-alanyl residues also for the inverse conformation (-ω, -φ{symbol}, -ψ). However, structures with mixed l and d-residues are unlikely to occur, since they are not energetically favourable. When the four-fold symmetry is reduced to two-fold symmetry, the energy of the system increased appreciably, so that deviations from the highly symmetric structure with a four-fold axis are unlikely to occur. Similar studies made for cyclotetraglycyl indicate that this structure also has stable conformation with a four-fold symmetry axis. The conformational parameters (ω, φ{symbol}, ψ) for this conformation are (-9°, 83°, 129°). © 1968.