1H-Azepine-4-amino-4-carboxylic acid: a new α,α-disubstituted ornithine analogue capable of inducing helix conformations in short Ala-Aib pentapeptides

Chemistry. 2012 Jul 9;18(28):8705-15. doi: 10.1002/chem.201104023. Epub 2012 Jun 11.

Abstract

A very efficient synthesis of orthogonally protected 1H-azepine-4-amino-4-carboxylic acid, abbreviated as Azn, a conformationally restricted analogue of ornithine, was realized. It was obtained on a gram scale in good overall yield in five steps, three of which did not require isolation of the intermediates, starting from the readily available 1-amino-4-oxo-cyclohexane-4-carboxylic acid. Both enantiomers were used for the preparation of pentapeptide models containing Ala, Aib, and Azn. Conformational studies using both spectroscopic techniques (NMR, CD) and molecular dynamics on model 5-mer peptides showed that the (R)-Azn isomer possesses a marked helicogenic effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azepines / chemistry*
  • Carboxylic Acids / chemistry*
  • Models, Molecular
  • Ornithine / analogs & derivatives*
  • Ornithine / chemistry*
  • Peptides / chemical synthesis*
  • Peptides / chemistry
  • Protein Conformation
  • Protein Structure, Secondary
  • Stereoisomerism

Substances

  • 1H-azepine-4-amino-4-carboxylic acid
  • Azepines
  • Carboxylic Acids
  • Peptides
  • Ornithine