ISSN:
0006-3525
Keywords:
nonpolar host peptides
;
310- and α-helix compatibilities of amino acids
;
determination of
;
CD spectroscopy
;
recorded at neutral, acidic, and basic pH
;
convex constraint CD
;
analysis according to G. Fasman
;
two-dimensional nmr spectroscopy, of 310- and α-helical conformations
;
x-ray spectroscopy, of 9-mer, 10-mer, and 12-mer peptides
;
optically pure (R)- and (S)-α,α-disubstituted amino acids
;
α- and β-tetralin derived amino acids
;
optically pure α-substituted aspartic and glutamic acid derivatives
;
optically pure α-substituted pyroglutamate and succinimide derivatives
;
Chemistry
;
Polymer and Materials Science
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
The present work describes three novel nonpolar host peptide sequences that provide a ready assessment of the 310- and α-helix compatibilities of natural and unnatural amino acids at different positions of small- to medium-size peptides. The unpolar peptides containing Ala, Aib, and a C-terminal p-iodoanilide group were designed in such a way that the peptides could be rapidly assembled in a modular fashion, were highly soluble in solvent mixtures of triflouroethanol and H2O for CD- and two-dimensional (2D) nmr spectroscopic analyses, and showed excellent crystallinity suited for x-ray structure analysis. To validate our approach we synthesized 9-mer peptides 79a-96 (Table IV), 12-mer peptides 99-110c (Table V), and 10-mer peptides 120a-125d and 129-133 (Table VI and Scheme 8) incorporating a series of optically pure cyclic and open-chain (R)- and (S)-α,α-disubstituted glycines 1-10 (Figure 2). These amino acids are known to significantly modulate the conformations of small peptides.Based on x-ray structures of 9-mers 79a, 80, and 87 (Figures 4-7), 10-mers 124c, 131, and 132 (Figures 9-12), and 12-mer peptide 102b (Figure 13), CD spectra of all peptides recorded in acidic, neutral, and basic media and detailed 2D-nmr analyses of 9-mer peptide 86 and 12-mer 102b, several interesting conformational observations were made. Especially interesting results were obtained using the convex constraint CD analysis proposed by Fasman on 9-mer peptides 79a-d, 80, 81, 86, and 87, which allowed us to determine the relative content of 310- and α-helical conformations. These results were fully supported by the corresponding x-ray and 2D-nmr analyses. As a striking example we found that the (S)- and (R)-β-tetralin derived amino acids (R)- and (S)-1 show excellent α-helix stabilisation, more pronounced than Aib and Ala. These novel reference peptide sequences should help establish a scale for natural and unnatural amino acids concerning their intrinsic 310- and α-helix compatibilities at different positions of medium-sized peptides and thus improve our understanding in the folding processes of peptides. © 1997 John Wiley & Sons, Inc. Biopoly 42: 575-626, 1997
Additional Material:
30 Ill.
Type of Medium:
Electronic Resource
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