Pseudo-prolines in cyclic peptides: Conformational stabilisation of cyclo[Pro-Thr(Ψ(Me,Me)pro)-Pro]

Article abstract of DOI:10.1016/S0040-4020(99)00650-X

Linear peptide H-Pro-Thr(Ψ(Me,Me)pro)-Pro-OH containing a preformed cis-Pro-Thr(Ψ(Me,Me)pro) tertiary amide bond cyclises instantaneously and free of formation of oligomeric structures to the cyclic tripeptide cyclo- [Pro-Thr(Ψ(Me,Me)pro)-Pro]. Even at concentrations up to 10^-1 M peptide, no oligomeric structures are detected by mass spectroscopy and HPLC. 2D ¹H NMR studies of purified cyclotripeptide reveal the compound to exist in one single conformation with all peptide bonds in the cis conformation. These results indicate enhanced cyclisation tendencies of cis-amide bond containing peptides of short chain length.