Synthesis and Solution Conformations of Cyclo(Pro-Leu-Gly)_2 and Cyclo(Pro-Leu-Gly)_4

摘要

Two cyclic peptides containing the C-terminal tripeptide sequence of oxytocin, cycl(Pro-Leu-Gly)_2 and cyclo-(Pro-Leu-Gly)_4, have been synthesized from the corresponding linear hexapeptide active ester under high dilution conditions. Cyclo(Pro-Leu-Gly)_4 serves as an exampled of the synthesis of cyclic peptides from linear peptides containing an even number of amino acid residues through dimerization. These two compounds are characterized by TLC, HPLC, amino acid analysis, MR, and mass spectra. Cyclo(Pro-Leu-Gly)_2 has also been synthesized from the linear tripeptide precursor independently, and its properties have been shown to be identical to that from linear hexapeptide. Circular dichroism indicated that cyclo(Pro-Leu-Gly)_2 contains #beta#-turns as expected; in contrast, cycl(Pro-Leu-Gly)_4 exhibited a random structure pattern. The MR spectra demonstrated that cyclo(Pro-Leu-Gly)_2 is fixed in only one conformer in DMSO, while in a CDCl_3 solution, several conformations with a rapid interconversion are present. Unlike the cyclohexapeptide, cycl(Pro-Leu-Gly)_4 showed more complicated NMR spectra in the two solvents; two or more conformers are considered to be present.