Synthesis and conformation of the cyclic octapeptides cyclo(Phe‐Pro)4, cyclo(Leu‐Pro)4, and cyclo[Lys(Z)‐Pro]4

Cyclic octapeptides, cyclo(X‐Pro)4, where X represents Phe, Leu, or Lys(Z), were synthesized and their conformations investigated. A C2‐symmetric conformer containing two cis peptide bonds was found in all of these cyclic octapeptides. The numbers of available conformations due to the cis–trans isomerization of Pro peptide bonds depended on the nature of the solvent and X residue: they decreased in the following order: cyclo[Lys(Z)‐Pro]4 > cyclo(Leu‐Pro)4 > cyclo(Phe‐Pro)4 in CDCl3. 13C spin‐lattice relaxation times (T1) of these cyclic octapeptides were measured, and the contribution of segmental mobility to T1 was found to vary with the nature of the X residue.