Solid-Phase Synthesis of β-Oligopeptides

Abstract

Fmoc-N-Protected β-amino acids of (S)-configuration bearing the side chains of Ala, Val, Leu, and Phe in the 3- and 2-position have been prepared. Manual solid-phase synthesis (ortho-chlorotrityl-chloride resin) of the β-heptapeptides H-β³-HVal-β³-HAla-β³-HLeu-β³-HPhe-β³-HVal-β³-HAla-β³-HLeu-OH and H-β²-HVal-β²-HAla-β²-HLeu-β²-HPhe-β²-HVal-β²-HAla-β²-HLeu-OH, and, for comparison, of the corresponding α-heptapeptide H-Val-Ala-Leu-Phe-Val-Ala-Leu-OH was achieved under standard conditions (HPLC/NMR identification). With H-β³-HVal-β³-HAla-β³-HLeu-β³-HPhe-β³-HVal-β³-HAla-β³-HLeu-OH, the yield and purity of the crude product are similar to those of H-Val-Ala-Leu-Phe-Val-Ala-Leu-OH, while the β² synthesis needs to be optimized. CD measurements show that the β-peptides have helical secondary structures in MeOH, while the α-peptide does not.