AUTHOR=Oliva Francesco , Bucci Raffaella , Tamborini Lucia , Pieraccini Stefano , Pinto Andrea , Pellegrino Sara 

TITLE=Bicyclic Pyrrolidine-Isoxazoline γ Amino Acid: A Constrained Scaffold for Stabilizing α-Turn Conformation in Isolated Peptides

JOURNAL=Frontiers in Chemistry

VOLUME=7

YEAR=2019

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2019.00133

DOI=10.3389/fchem.2019.00133

ISSN=2296-2646

ABSTRACT=<p>Unnatural amino acids have tremendously expanded the folding possibilities of peptides and peptide mimics. While α,α-disubstituted and β-amino acids are widely studied, γ-derivatives have been less exploited. Here we report the conformational study on the bicyclic unnatural γ amino acid, 4,5,6,6a-tetrahydro-3a<italic>H</italic>-pyrrolo[3,4-d]isoxazole-3-carboxylic acid <bold>1</bold>. In model peptides, the (+)-(3a<italic>R</italic>6a<italic>S</italic>)-enantiomer is able to stabilize α-turn conformation when associated to glycine, as showed by <sup>1</sup>H-NMR, FT-IR, and circular dichroism experiments, and molecular modeling studies. α-turn is a structural motif occurring in many biologically active protein sites, although its stabilization on isolated peptides is quite uncommon. Our results make the unnatural γ-amino acid <bold>1</bold> of particular interest for the development of bioactive peptidomimetics.</p>