Syntheses and CD-spectroscopic investigations of longer-chain β-peptides:: Preparation by solid-phase couplings of single amino acids, dipeptides, and tripeptides

The synthesis and CD-spectroscopic analysis of eleven water-soluble beta-peptides composed of all-beta(3) or alternating beta(2)- and beta(3)-amino acids is described. Different approaches for the efficient syntheses of longer-chain beta-peptides (> 9 residues) were investigated. They were synthesized on solid phase with Fmoc-protected amino acids or Fmoc-protected di- or tripeptide fragments (assembled using solution-phase synthesis). The use of preformed fragments significantly increased the purity of the crude peptides and facilitated purification. Epecially, the use of Fmoc-protected beta(2)/beta(3)-dipeptides for the synthesis of a 'mixed' beta(2)/beta(3)-nonapeptide proved to be remarkably effective, yielding the crude peptide in 95% purity and without detectable epimerization of the beta(2)-amino acid residues. This is a significant improvement over previously reported procedures for the solid-phase synthesis of beta-peptides, and foreshadows that the field of beta-peptide research will now switch from synthesis to the design and study of complex functional 'beta-proteins'.