1H-Azepine-2-oxo-5-amino-5-carboxylic Acid: A 3(10) Helix Inducer and an Effective Tool for Functionalized Gold Nanoparticles

A new alpha,alpha-disubstituted constrained glutamine analogue has been designed to decorate gold nanopartides and to induce a 3(10)-helix when inserted in peptides. Using an efficient "one-pot" asymmetric Schmidt reaction between 4-disubstituted-cydohexanone 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 3(10)-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 nanopartides.