1H-Azepine-2-oxo-5-amino-5-carboxylic Acid: A 310 Helix Inducer and an Effective Tool for Functionalized Gold Nanoparticles

A new α,α-disubstituted constrained glutamine analogue has been designed to decorate gold nanoparticles and to induce a 3₁₀-helix when inserted in peptides. Using an efficient “one-pot” asymmetric Schmidt reaction between 4-disubstituted-cyclohexanone and hydroxyalkylazides, 1H-azepine-2-oxo-5-amino-5-carboxylic acid was prepared. The main (R) isomer was inserted at the N-terminus in a very short peptide sequence (i.e., PhCO-(R)-Oxo-Azn-l-Ala-Aib-l-AlaNHMe) and a stable 3₁₀-helix conformation was obtained, as verified by both NMR experiments and molecular dynamics (MD) simulations. Finally, the presence of the hydroxyl chain at the nitrogen atom of the ring allowed for the preparation of covered chiral gold nanoparticles.

J. Org. Chem., 2015, 80 (11), pp 5507–5516
DOI: 10.1021/acs.joc.5b00396