Applications of biaryl cyclization in the synthesis of cyclic enkephalin analogs with a highly restricted flexibility
Abstract A series of 10 cyclic, biaryl analogs of enkephalin, with Tyr or Phe residues at positions 1 and 4, were synthesized according to the Miyaura borylation and Suzuki coupling methodology. Biaryl bridges formed by side chains of the two aromatic amino acid residues are of the meta–meta, meta–p...
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Springer
2024-03-01
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| Series: | Amino Acids |
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| Online Access: | https://doi.org/10.1007/s00726-023-03371-5 |
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| author | Maria Różanowska Gabriela Szczupaj Michał Nowakowski Priyadharshni Rajagopal Piotr F. J. Lipiński Joanna Matalińska Aleksandra Misicka Marek Lisowski Łukasz Jaremko Mariusz Jaremko |
| author_facet | Maria Różanowska Gabriela Szczupaj Michał Nowakowski Priyadharshni Rajagopal Piotr F. J. Lipiński Joanna Matalińska Aleksandra Misicka Marek Lisowski Łukasz Jaremko Mariusz Jaremko |
| author_sort | Maria Różanowska |
| collection | DOAJ |
| description | Abstract A series of 10 cyclic, biaryl analogs of enkephalin, with Tyr or Phe residues at positions 1 and 4, were synthesized according to the Miyaura borylation and Suzuki coupling methodology. Biaryl bridges formed by side chains of the two aromatic amino acid residues are of the meta–meta, meta–para, para–meta, and para–para configuration. Conformational properties of the peptides were studied by CD and NMR. CD studies allowed only to compare conformations of individual peptides while NMR investigations followed by XPLOR calculations provided detailed information on their conformation. Reliability of the XPLOR calculations was confirmed by quantum chemical ones performed for one of the analogs. No intramolecular hydrogen bonds were found in all the peptides. They are folded and adopt the type IV β-turn conformation. Due to a large steric strain, the aromatic carbon atoms forming the biaryl bond are distinctly pyramidalized. Seven of the peptides were tested in vitro for their affinity for the µ-opioid receptor. |
| format | Article |
| id | doaj-art-7913d3d3390d40c8aa6a31bafe836ff2 |
| institution | Kabale University |
| issn | 1438-2199 |
| language | English |
| publishDate | 2024-03-01 |
| publisher | Springer |
| record_format | Article |
| series | Amino Acids |
| spelling | doaj-art-7913d3d3390d40c8aa6a31bafe836ff22024-12-22T12:34:17ZengSpringerAmino Acids1438-21992024-03-0156111710.1007/s00726-023-03371-5Applications of biaryl cyclization in the synthesis of cyclic enkephalin analogs with a highly restricted flexibilityMaria Różanowska0Gabriela Szczupaj1Michał Nowakowski2Priyadharshni Rajagopal3Piotr F. J. Lipiński4Joanna Matalińska5Aleksandra Misicka6Marek Lisowski7Łukasz Jaremko8Mariusz Jaremko9Faculty of Chemistry, University of WrocławFaculty of Chemistry, Biological and Chemical Research Centre, University of WarsawFaculty of Chemistry, Biological and Chemical Research Centre, University of WarsawBioscience Program, Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST)Department of Neuropeptides, Mossakowski Medical Research Institute, Polish Academy of SciencesDepartment of Neuropeptides, Mossakowski Medical Research Institute, Polish Academy of SciencesDepartment of Neuropeptides, Mossakowski Medical Research Institute, Polish Academy of SciencesFaculty of Chemistry, University of WrocławBioscience Program, Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST)Bioscience Program, Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST)Abstract A series of 10 cyclic, biaryl analogs of enkephalin, with Tyr or Phe residues at positions 1 and 4, were synthesized according to the Miyaura borylation and Suzuki coupling methodology. Biaryl bridges formed by side chains of the two aromatic amino acid residues are of the meta–meta, meta–para, para–meta, and para–para configuration. Conformational properties of the peptides were studied by CD and NMR. CD studies allowed only to compare conformations of individual peptides while NMR investigations followed by XPLOR calculations provided detailed information on their conformation. Reliability of the XPLOR calculations was confirmed by quantum chemical ones performed for one of the analogs. No intramolecular hydrogen bonds were found in all the peptides. They are folded and adopt the type IV β-turn conformation. Due to a large steric strain, the aromatic carbon atoms forming the biaryl bond are distinctly pyramidalized. Seven of the peptides were tested in vitro for their affinity for the µ-opioid receptor.https://doi.org/10.1007/s00726-023-03371-5CyclizationBiaryl bridges in peptidesMiyaura–Suzuki reactionNMRCDMolecular docking |
| spellingShingle | Maria Różanowska Gabriela Szczupaj Michał Nowakowski Priyadharshni Rajagopal Piotr F. J. Lipiński Joanna Matalińska Aleksandra Misicka Marek Lisowski Łukasz Jaremko Mariusz Jaremko Applications of biaryl cyclization in the synthesis of cyclic enkephalin analogs with a highly restricted flexibility Amino Acids Cyclization Biaryl bridges in peptides Miyaura–Suzuki reaction NMR CD Molecular docking |
| title | Applications of biaryl cyclization in the synthesis of cyclic enkephalin analogs with a highly restricted flexibility |
| title_full | Applications of biaryl cyclization in the synthesis of cyclic enkephalin analogs with a highly restricted flexibility |
| title_fullStr | Applications of biaryl cyclization in the synthesis of cyclic enkephalin analogs with a highly restricted flexibility |
| title_full_unstemmed | Applications of biaryl cyclization in the synthesis of cyclic enkephalin analogs with a highly restricted flexibility |
| title_short | Applications of biaryl cyclization in the synthesis of cyclic enkephalin analogs with a highly restricted flexibility |
| title_sort | applications of biaryl cyclization in the synthesis of cyclic enkephalin analogs with a highly restricted flexibility |
| topic | Cyclization Biaryl bridges in peptides Miyaura–Suzuki reaction NMR CD Molecular docking |
| url | https://doi.org/10.1007/s00726-023-03371-5 |
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