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.
†Dipartimento di Scienze Farmaceutiche- Sezione di Chimica Generale e Organica- "A. Marchesini" Università degli Studi di Milano, Via Venezian 21 20133, Milano, Italy.
Sara
S
Pellegrino
†Dipartimento di Scienze Farmaceutiche- Sezione di Chimica Generale e Organica- "A. Marchesini" Università degli Studi di Milano, Via Venezian 21 20133, Milano, Italy.
Andrea
A
Bonetti
†Dipartimento di Scienze Farmaceutiche- Sezione di Chimica Generale e Organica- "A. Marchesini" Università degli Studi di Milano, Via Venezian 21 20133, Milano, Italy.
Francesca
F
Clerici
†Dipartimento di Scienze Farmaceutiche- Sezione di Chimica Generale e Organica- "A. Marchesini" Università degli Studi di Milano, Via Venezian 21 20133, Milano, Italy.
Alessandro
A
Contini
§Dipartimento di Scienze Chimiche, Università degli Studi di Padova, Via Marzolo 1 35131, Padova, Italy.
Alessandro
A
Moretto
‡CNR- Istituto di Scienze e Tecnologie Molecolari, Via Golgi 19 20133, Milano, Italy.
Raffaella
R
Soave
†Dipartimento di Scienze Farmaceutiche- Sezione di Chimica Generale e Organica- "A. Marchesini" Università degli Studi di Milano, Via Venezian 21 20133, Milano, Italy.
Maria Luisa
ML
Gelmi
D000595:Amino Acid Sequence; D001381:Azepines / Q000138:chemical synthesis / Q000737:chemistry*; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D006046:Gold / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D013237:Stereoisomerism
C000605293:1H-azepine-2-oxo-5-amino-5-carboxylic Acid; D001381:Azepines; D002264:Carboxylic Acids; D010455:Peptides; D006046:Gold