Multiple conformational equilibria of cyclic octapeptide,cyclo (L-Pro-Sar)4 in solution

Cyclo (l -Pro-Sar)₄ is asynthetic cyclic octapeptide composed of only N -substituted amino acids. The conformation of this peptide in different solvents was examined by ¹H-and ¹³C-n.m.r. spectroscopy, ¹H-n.m.r. data of this cyclic peptide demonstrated that multiple conformational equilibria take place in solution and they vary with solvent polarity. Three conformers are interconverting with each other in the nonpolar chloroform (CDCl₃); one C₄-symmetric conformer (49%) and two C₂-symmetric conformers (37% and 14%). While three C₂-symmetric (59%, 19%, and 18%) and one asymmetric conformer (4%) are detected to coexist in acetonitrile (CD₃CN), one largely populated C₂-symmetric one (97%) is favored in the polar dimethyl sulfoxide (Me₂SO-d ₆). N.m.r. measurement employing various strategy predicted the occurrence of trans-cis-cis-cis-trans-cis-cis-cis (two Sar-Pro bonds: trans) (tccctccc) peptide bond sequence in a predominant C₂-symmetric conformer of Me₂SO-d ₆ solution. In the same way, tccctccc and ctttcttt (two Sar-Pro bonds: cis) peptide unit arrangement was proposed for the first and the secondly populated conformer in CD₃CN, respectively. In CDCl₃ a conformer having tctctctc (four Sar-Pro bonds: trans) C₄-symmetric peptide bond sequence was deduced.