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

摘要

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. Especially, 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 fiel of beta-peptide research will now switch from synthesis to the design and study of complex functional 'beta-proteins.'