Premium
Synthesis, CD Spectra, and Enzymatic Stability of β 2 ‐Oligoazapeptides Prepared from ( S )‐2‐Hydrazino Carboxylic Acids Carrying the Side Chains of Val, Ala, and Leu
Author(s) -
Lelais Gérald,
Seebach Dieter
Publication year - 2003
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200390342
Subject(s) - chemistry , tripeptide , stereochemistry , nuclear magnetic resonance spectroscopy , amino acid , peptide , heteroatom , side chain , nmr spectra database , peptide synthesis , reagent , protein secondary structure , circular dichroism , organic chemistry , spectral line , ring (chemistry) , biochemistry , physics , astronomy , polymer
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 β 2 ‐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‐ β 2 ‐amino acids and a corresponding tripeptide ( N ‐Boc/ C ‐OMe strategy) with common peptide‐coupling reagents in solution led to β 2 ‐di, β 2 ‐tri‐, and β 2 ‐hexaazapeptide derivatives, which could be N ‐debenzylated ( 4 – 9 ; Schemes 2–4 ). The new compounds were identified by optical rotation, and IR, 1 H‐ and 13 C‐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 the β 2 ‐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 H 2 O (at different pH) might arise from a ( P )‐ 3 14 ‐helical structure. The N ‐Boc‐ β 2 ‐tri and N ‐Boc‐ β 2 ‐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.