Pellegrino Sara, Bonetti Andrea, Clerici Francesca, Contini Alessandro, Moretto Alessandro, Soave Raffaella, Gelmi Maria Luisa
†Dipartimento di Scienze Farmaceutiche- Sezione di Chimica Generale e Organica- "A. Marchesini" Università degli Studi di Milano, Via Venezian 21 20133, Milano, Italy.
§Dipartimento di Scienze Chimiche, Università degli Studi di Padova, Via Marzolo 1 35131, Padova, Italy.
J Org Chem. 2015 Jun 5;80(11):5507-16. doi: 10.1021/acs.joc.5b00396. Epub 2015 May 14.
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.
