Title
Synthesis, CD Spectra, and Enzymatic Stability of β2-Oligoazapeptides Prepared from (S)-2-Hydrazino Carboxylic Acids Carrying the Side Chains of Val, Ala, and Leu
Author
Gérald Lelais, Dieter Seebach
Year
2003
Journal
Helvetica Chimica Acta
Abstract
β-Peptides offer the unique possibility to incorporate additional heteroatoms into the peptidic backbone (Figs. 1 and 2). We report here the synthesis and spectroscopic investigations of β2-peptide analogs consisting of (S)-3-aza-β-amino acids carrying the side chains of Val, Ala, and Leu. The hydrazino carboxylic acids were prepared by a known method: Boc amidation of the corresponding N-benzyl-l-α-amino acids with an oxaziridine (Scheme 1). Couplings and fragment coupling of the 3-benzylaza-β2-amino acids and a corresponding tripeptide (N-Boc/C-OMe strategy) with common peptide-coupling reagents in solution led to β2-di, β2-tri-, and β2-hexaazapeptide derivatives, which could be N-debenzylated (4–9; Schemes 2–4). The new compounds were identified by optical rotation, and IR, 1H- and 13C-NMR, and CD spectroscopy (Figs. 4 and 5) and high-resolution mass spectrometry, and, in one case, by X-ray crystallography (Fig. 3). In spite of extensive measurements under various conditions (temperatures, solvents), it was not possible to determine the secondary structure of theβ2-azapeptides by NMR spectroscopy (overlapping and broad signals, fast exchange between the two types of NH protons!). The CD spectra of the N-Boc and C-OMe terminally protected hexapeptide analog 9 in MeOH and in H2O (at different pH) might arise from a (P)-314-helical structure. The N-Boc-β2-tri and N-Boc-β2-hexaazapeptide esters, 7 and 9, were shown to be stable for 48 h against the following peptidases: pronase, proteinase K, chymotrypsin, trypsin, carboxypeptidase A, and 20S proteasome.
Instrument
J-710
Keywords
Circular dichroism, Secondary structure, Biochemistry