NMR-solution structures in methanol of an α-heptapeptide, of a β32-nonapeptide, and of an all-β3-icosapeptide carrying the 20 proteinogenic side chains

Dieter Seebach*, Raveendra I. Mathad, Thierry Kimmerlin, Yogesh R. Mahajan, Pascal Bindschädler, Magnus Rueping, Bernhard Jaun, Christian Hilty, Touraj Etezady-Esfarjani

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

The NMR-solution structure of an α-heptapeptide with a central Aib residue was investigated in order to verify that, in contrast to β-peptides, short α-peptides do not form a helical structures in MeOH. Although the central Aib residue was found to induce a bend in the experimentally determined structure, no secondary structure typical for longer α-peptides or proteins was found. A β23- nonapeptide with polar, positively charged side chains was subjected to NMR analysis in MeOH and H2O. Whereas, in MeOH, it folds into a 10/12-helix very similar to the structure determined for a corresponding β23-nonapeptide with only aliphatic side chains, no dominant conformation could be determined in H2O. Finally, the NMR analysis of a β3-icosapeptide containing the side chains of all 20 proteinogenic amino acids in MeOH is described. It revealed that this 20mer folds into a 314-helix over its whole length forming six full turns, the longest 314-helix found so far. Together, our findings confirm that, in contrast to α-peptides, β-peptides not only form helices with just six residues, but also form helices that are longer than helical sections usually observed in proteins or natural peptides. The higher helix-forming propensity of long β-peptides is attributed to the conformation-stabilizing effect of the staggered ethane sections in β-peptides which outweighs the detrimental effect of the increasing macrodipole.

Original languageEnglish (US)
Pages (from-to)1969-1982
Number of pages14
JournalHelvetica Chimica Acta
Volume88
Issue number7
DOIs
StatePublished - Aug 11 2005

ASJC Scopus subject areas

  • Catalysis
  • Biochemistry
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Fingerprint

Dive into the research topics of 'NMR-solution structures in methanol of an α-heptapeptide, of a β<sup>3</sup>/β<sup>2</sup>-nonapeptide, and of an all-β<sup>3</sup>-icosapeptide carrying the 20 proteinogenic side chains'. Together they form a unique fingerprint.

Cite this