Bicyclic Pyrrolidine-Isoxazoline γ Amino Acid: A Constrained Scaffold for Stabilizing α-Turn Conformation in Isolated Peptides
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-te...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-03-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fchem.2019.00133/full |
| _version_ | 1811292051576193024 |
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| author | Francesco Oliva Raffaella Bucci Lucia Tamborini Stefano Pieraccini Andrea Pinto Sara Pellegrino |
| author_facet | Francesco Oliva Raffaella Bucci Lucia Tamborini Stefano Pieraccini Andrea Pinto Sara Pellegrino |
| author_sort | Francesco Oliva |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T04:39:39Z |
| format | Article |
| id | doaj.art-73d2bfa42264473cb4994aa649c83d9d |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-04-13T04:39:39Z |
| publishDate | 2019-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-73d2bfa42264473cb4994aa649c83d9d2022-12-22T03:02:03ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462019-03-01710.3389/fchem.2019.00133439669Bicyclic Pyrrolidine-Isoxazoline γ Amino Acid: A Constrained Scaffold for Stabilizing α-Turn Conformation in Isolated PeptidesFrancesco Oliva0Raffaella Bucci1Lucia Tamborini2Stefano Pieraccini3Andrea Pinto4Sara Pellegrino5Department of Chemistry, University of Milan, Milan, ItalyDepartment of Pharmaceutical Sciences, University of Milan, Milan, ItalyDepartment of Pharmaceutical Sciences, University of Milan, Milan, ItalyDepartment of Chemistry, University of Milan, Milan, ItalyDepartment of Food, Environmental and Nutritional Sciences, University of Milan, Milan, ItalyDepartment of Pharmaceutical Sciences, University of Milan, Milan, ItalyUnnatural 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.https://www.frontiersin.org/article/10.3389/fchem.2019.00133/fullunnatural γ-amino acidspeptidomimeticisoxazolineα-turnmetadynamic studiesconformational analysis |
| spellingShingle | Francesco Oliva Raffaella Bucci Lucia Tamborini Stefano Pieraccini Andrea Pinto Sara Pellegrino Bicyclic Pyrrolidine-Isoxazoline γ Amino Acid: A Constrained Scaffold for Stabilizing α-Turn Conformation in Isolated Peptides Frontiers in Chemistry unnatural γ-amino acids peptidomimetic isoxazoline α-turn metadynamic studies conformational analysis |
| title | Bicyclic Pyrrolidine-Isoxazoline γ Amino Acid: A Constrained Scaffold for Stabilizing α-Turn Conformation in Isolated Peptides |
| title_full | Bicyclic Pyrrolidine-Isoxazoline γ Amino Acid: A Constrained Scaffold for Stabilizing α-Turn Conformation in Isolated Peptides |
| title_fullStr | Bicyclic Pyrrolidine-Isoxazoline γ Amino Acid: A Constrained Scaffold for Stabilizing α-Turn Conformation in Isolated Peptides |
| title_full_unstemmed | Bicyclic Pyrrolidine-Isoxazoline γ Amino Acid: A Constrained Scaffold for Stabilizing α-Turn Conformation in Isolated Peptides |
| title_short | Bicyclic Pyrrolidine-Isoxazoline γ Amino Acid: A Constrained Scaffold for Stabilizing α-Turn Conformation in Isolated Peptides |
| title_sort | bicyclic pyrrolidine isoxazoline γ amino acid a constrained scaffold for stabilizing α turn conformation in isolated peptides |
| topic | unnatural γ-amino acids peptidomimetic isoxazoline α-turn metadynamic studies conformational analysis |
| url | https://www.frontiersin.org/article/10.3389/fchem.2019.00133/full |
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