BETA-PEPTIDES - SYNTHESIS BY ARNDT-EISTERT HOMOLOGATION WITH CONCOMITANT PEPTIDE COUPLING - STRUCTURE DETERMINATION BY NMR AND CD SPECTROSCOPY AND BY X-RAY CRYSTALLOGRAPHY - HELICAL SECONDARY STRUCTURE OF A BETA-HEXAPEPTIDE IN SOLUTION AND ITS STABILITY TOWARDS PEPSIN
D. Seebach et al., BETA-PEPTIDES - SYNTHESIS BY ARNDT-EISTERT HOMOLOGATION WITH CONCOMITANT PEPTIDE COUPLING - STRUCTURE DETERMINATION BY NMR AND CD SPECTROSCOPY AND BY X-RAY CRYSTALLOGRAPHY - HELICAL SECONDARY STRUCTURE OF A BETA-HEXAPEPTIDE IN SOLUTION AND ITS STABILITY TOWARDS PEPSIN, Helvetica Chimica Acta, 79(4), 1996, pp. 913-941
The beta-hexapeptide (H-beta-HVal-beta-HAla-beta-HLeu)(2)-OH (2) was p
repared from the component L-beta-amino acids by conventional peptide
synthesis, including fragment coupling. A cyclo-beta-tri- and a cyclo-
beta-hexapeptide were also prepared. The beta-amino acids were obtaine
d from alpha-amino acids by Arndt-Eistert homologation. All reactions
leading to the beta-peptides occur smoothly and in high yields. The be
ta-peptides were characterized by their CD and NMR spectra (COSY, ROES
Y, TOCSY, and NOE-restricted modelling), and by an X-ray crystal-struc
ture analysis. beta-Sheet-type structures (in the solid state) and a c
ompact, left-handed or (M) 3(1) helix of 5-Angstrom pitch (in solution
) were discovered. Comparison with the analogous secondary structures
of alpha-peptides shows fundamental differences, the most surprising o
ne at this point being the greater stability of beta-peptide helices.
There are structural relationships of beta-peptides with oligomers of
beta-hydroxyalkanoic acids, and dissimilarities between the two classe
s of compounds are a demonstration of the power of H-bonding. The beta
-hexapeptide 2 is stable to cleavage by pepsin at pH 2 in H2O for at l
east 60 h at 37 degrees, while the corresponding alpha-peptide H-(Val-
Ala-Leu)(2)-OH is cleaved instantaneously under these conditions. The
implication of the described results are discussed.