Folding of a linear array of α-amino acids within a helical aromatic oligoamide frame

J Am Chem Soc. 2013 Jul 3;135(26):9628-31. doi: 10.1021/ja404656z. Epub 2013 Jun 24.

Abstract

Control of the spatial organization of proteinogenic side chains is critical for the development of protein mimics with selective recognition properties toward target protein surfaces. We present a novel methodology for producing a linear array of proteinogenic residues based on the incorporation of α-amino acids into sequences of rigid, helically folded oligoamides of 8-amino-2-quinolinecarboxylic acid (Q). When L-leucine (L) was alternated with dimer Q2, the resulting sequence adopted a right-handed helical conformation, as deduced in solution from the CD spectra of L-(LQ2)n (n = 2, 4) and in the solid state from X-ray crystallographic analysis of (±)-(LQ2)4. Each LQ2 segment spanned just one helix turn (pitch of 3.5 Å), and consequently, the four leucine side chains of (LQ2)4 formed a linear array. In solution, NMR analysis showed that both L-(LQ2)2 and L-(LQ2)4 exist as a mixture of two slowly equilibrating folded conformers, the proportion of which strongly varies with the solvent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry*
  • Leucine / chemistry*
  • Molecular Structure
  • Quinolines / chemistry*

Substances

  • 8-amino-2-quinoline carboxylic acid
  • Amides
  • Quinolines
  • Leucine