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-3aH-pyrrolo[3,4-d]isoxazole-3-carboxylic acid 1. In model peptides, the (+)-(3aR6aS)-enantiomer is able to stabilize α-turn conformation when associated to glycine, as showed by 1H-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 1 of particular interest for the development of bioactive peptidomimetics.
Bicyclic Pyrrolidine-Isoxazoline γ Amino Acid : A Constrained Scaffold for Stabilizing α-Turn Conformation in Isolated Peptides / F. Oliva, R. Bucci, L. Tamborini, S. Pieraccini, A. Pinto, S. Pellegrino. - In: FRONTIERS IN CHEMISTRY. - ISSN 2296-2646. - 7(2019 Mar 18), pp. 133.1-133.10. [10.3389/fchem.2019.00133]
Bicyclic Pyrrolidine-Isoxazoline γ Amino Acid : A Constrained Scaffold for Stabilizing α-Turn Conformation in Isolated Peptides
F. Oliva;R. Bucci;L. Tamborini;S. Pieraccini;A. Pinto;S. Pellegrino
2019
Abstract
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-3aH-pyrrolo[3,4-d]isoxazole-3-carboxylic acid 1. In model peptides, the (+)-(3aR6aS)-enantiomer is able to stabilize α-turn conformation when associated to glycine, as showed by 1H-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 1 of particular interest for the development of bioactive peptidomimetics.File | Dimensione | Formato | |
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