S. Vijayalakshmi et al., Comparison of helix-stabilizing effects of alpha,alpha-dialkyl glycines with linear and cycloalkyl side chains, BIOPOLYMERS, 53(1), 2000, pp. 84-98
The ability of tr,alpha,alpha-di-n-alkyl glycines with linear and cyclic al
kyl side chains to stabilize helical conformations has been compared rasing
a model heptapeptide sequence. The conformations of five synthetic heptape
ptides (Boc-Val-Ala-Leu-Xxx-Val-Ala-Leu-OMe, Xxx = Ac(8)c, Ac(7)c, Aib, Dpg
, and Deg, where Ac(8)c = 1-aminocycloactane-1-carboxylic acid, Ac(7)c =1-a
minocycloheptane-1-carboxylic acid; Aib = alpha-aminoisobutyric acid, Dpg =
alpha,alpha-di-n-propyl glycine, Deg = alpha,alpha-di-n-ethyl glycine) hav
e been investigated. In crystals, helical conformations have been demonstra
ted by x-ray crystallography for the peptides, R-Val-Ala-Leu-Dpg-Val-Ala-Le
u-OMe, (R = Boc and acetyl). Solution conformations of the five peptides ha
ve been studied by H-1-nmr. In the apolar solvent CDCl3, all five peptides
favor helical conformations in which the NH groups of residues 3-7 are shie
lded from the solvent Successive NiH <----> Ni+1H nuclear Overhauser effect
s over the length of the sequence support a major population of continuous
helical conformations. Solvent titration experiments in mixtures of CDCl3/D
MSO provide evidence for solvent-dependent conformational transitions that
are more pronounced for the Deg and Dpg peptides. Solvent-dependent chemica
l shift variations and temperature coefficients in DMSO suggest that the co
nformational distributions in title Deg/Dpg peptides are distinctly differe
nt from the Aib/Ac(n)c peptides in a strongly solvating medium. Nuclear Ove
rhauser effects provide additional evidence for the population of extended
backbone conformations in the Dpg peptide, while a significant residual pop
ulation of helical conformations is still detectable in the isomeric Ac(7)c
peptide in DMSO. (C) 2000 John Wiley & Sons, Inc.