SOLID-PHASE SYNTHESES OF PEPTOIDS USING FMOC-PROTECTED N-SUBSTITUTED GLYCINES - THE SYNTHESIS OF (RETRO) PEPTOIDS OF LEU-ENKEPHALIN AND SUBSTANCE-P

A particularly interesting class of oligomeric peptidomimetics is form ed by the peptoids, which consist of N-substituted glycine residues. A solid-phase synthesis method for peptoids is presented in which these residues are introduced using their Fmoc derivatives. This ''monomer' ' method allowed the monitored synthesis of relatively large quantitie s of pure peptoids as well as the translation of, in principle, any pe ptide into the corresponding peptoid. The required Fmoc-substituted gl ycines were accessible by convenient synthesis, and a number of monome rs including those containing side chains with functional groups have been synthesized. The use of Fmoc monomers also allowed implementation of a solid-phase synthesis protocol on a commercial peptide synthesiz er. The method was exemplified by the solid-phase syntheses of the (re tro)peptoids of Leu-enkephalin and substance P. Mass spectrometric stu dies of (retro)peptoids were essential for their characterization, and the presence of the B- and Y ''- type ions allows sequence analysis. Substance P (retro)-peptoids were biologically active. HPLC analysis s howed an increased hydrophobicity, and pepsin treatment resulted in gr eatly reduced degradation compared with the corresponding peptide.