Comparative α-helicity of cyclic pentapeptides in water

Angew Chem Int Ed Engl. 2014 Jul 1;53(27):6965-9. doi: 10.1002/anie.201310245. Epub 2014 May 14.

Abstract

Helix-constrained polypeptides have attracted great interest for modulating protein-protein interactions (PPI). It is not known which are the most effective helix-inducing strategies for designing PPI agonists/antagonists. Cyclization linkers (X1-X5) were compared here, using circular dichroism and 2D NMR spectroscopy, for α-helix induction in simple model pentapeptides, Ac-cyclo(1,5)-[X1-Ala-Ala-Ala-X5]-NH2, in water. In this very stringent test of helix induction, a Lys1→Asp5 lactam linker conferred greatest α-helicity, hydrocarbon and triazole linkers induced a mix of α- and 3₁₀-helicity, while thio- and dithioether linkers produced less helicity. The lactam-linked cyclic pentapeptide was also the most effective α-helix nucleator attached to a 13-residue model peptide.

Keywords: NMR structure; circular dichroism; cyclic peptides; helix induction; α-helix.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Circular Dichroism
  • Magnetic Resonance Spectroscopy
  • Oligopeptides / chemistry*
  • Peptides, Cyclic / chemistry*
  • Protein Structure, Secondary
  • Temperature
  • Water / chemistry*

Substances

  • Oligopeptides
  • Peptides, Cyclic
  • Water