Spectroscopic detection of pseudo-turns in homodetic cyclic penta- and hexapeptides comprising β-homoproline

Miroslav Malešević, Zsuzsanna Majer, Elemér Vass, Thomas Huber, Ulf Strijowski, Miklós Hollósi, Norbert Sewald

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14 Citations (Scopus)

Abstract

β-Amino acids with side chains at C2 and/or at C 3 are of growing interest in drug design, as they may induce astonishing and unusual peptide conformations. Therefore it is of eminent importance to gather information on the consequences of β-amino acid incorporation on the three-dimensional structure of a peptide. This paper describes the synthesis and conformational analysis of cyclic penta- and hexapeptides comprising either (S)-Pro or (S)-β-Hpro. The conformational influence of the β-homoproline building block was analyzed by the combined application of CD, FT-IR and NMR. While the CD spectra of the proline containing peptides indicate the presence of inverse γ-turns and βII-turns, the CD spectra of the β-homoamino acid analogs are dominated by an unprecedented negative band near 205 nm associated with a pseudo-β-turn (Ψβ) or pseudo-γ-turn (Ψγ). These results were confirmed by FT-IR spectroscopy, which also indicates the formation of two internal hydrogen bonds in the cyclic peptides containing the β-homoproline. The conformations of the β-homoproline containing pentapeptides were additionally determined by NMR in combination with MD simulations in two different solvents. The conformation in trifluoroethanol (TFE) is characterized by a bifurcated hydrogen bond stabilizing a pseudo-γ-turn with β-homoproline in the central position, nested with a pseudo-β-turn with β-homoproline in the i+1 position. The combined CD/FT-IR studies clearly show that the replacement of proline by β-homoproline gives rise to a more flexible peptide backbone, and CD spectroscopy hints towards the presence of pseudo-β- or pseudo-γ-turns.

Original languageEnglish
Pages (from-to)165-177
Number of pages13
JournalInternational Journal of Peptide Research and Therapeutics
Volume12
Issue number2
DOIs
Publication statusPublished - Jun 1 2006

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Keywords

  • CD, IR, NMR spectroscopy
  • Conformational analysis
  • Peptides
  • Turns

ASJC Scopus subject areas

  • Analytical Chemistry
  • Bioengineering
  • Biochemistry
  • Molecular Medicine
  • Drug Discovery

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