Synthesis, Hydrolytic Stability and In Vivo Biological Study of Bioconjugates of the Tetrapeptides FELL Containing Pyrrole Moiety
Background: Bioconjugates are promising alternatives for the multiple targeting of any disease. Pyrrole heterocycle is well known with many activities and is a building block of a lot of medical drugs. On the other hand, peptides are short molecules with many advantages such as small size, ability t...
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MDPI AG
2023-12-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/12/3265 |
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| author | Boryana Borisova Stanislava Vladimirova Hristina Nocheva Marie Laronze-Cochard Stéphane Gérard Stoyko Petrin Dancho Danalev |
| author_facet | Boryana Borisova Stanislava Vladimirova Hristina Nocheva Marie Laronze-Cochard Stéphane Gérard Stoyko Petrin Dancho Danalev |
| author_sort | Boryana Borisova |
| collection | DOAJ |
| description | Background: Bioconjugates are promising alternatives for the multiple targeting of any disease. Pyrrole heterocycle is well known with many activities and is a building block of a lot of medical drugs. On the other hand, peptides are short molecules with many advantages such as small size, ability to penetrate the cell membrane and bond-specific receptors, vectorizing potential, etc. Thus, hybrid molecules between peptide and pyrrole moiety could be a promising alternative as an anti-pain tool. Methods: New bioconjugates with a general formula Pyrrole (α-/β-acid)-FELL-OH (NH<sub>2</sub>) were synthesized using Fmoc/OtBu peptide synthesis on solid support. HPLC was used to monitor the purity of newly synthesized bioconjugates. Their structures were proven by electrospray ionization mass spectrometry. The Paw Pressure test (Randall–Selitto test) was used to examinate the analgesic activity. Hydrolytic stability of targeted structures was monitored in three model systems with pH 2.0, 7.4 and 9.0, including specific enzymes by means of the HPLC-UV method. Results: The obtained results reveal that all newly synthesized bioconjugates have analgesic activity according to the used test but free pyrrole acids have the best analgesic activity. Conclusions: Although free pyrrole acids showed the best analgesic activity, they are the most unstable for hydrolysis. Combination with peptide structure leads to the hydrolytic stabilization of the bioconjugates, albeit with slightly reduced activity. |
| first_indexed | 2024-03-08T20:58:44Z |
| format | Article |
| id | doaj.art-84e7672d38bc4251819dbc8d3b8789a2 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-08T20:58:44Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-84e7672d38bc4251819dbc8d3b8789a22023-12-22T13:55:08ZengMDPI AGBiomedicines2227-90592023-12-011112326510.3390/biomedicines11123265Synthesis, Hydrolytic Stability and In Vivo Biological Study of Bioconjugates of the Tetrapeptides FELL Containing Pyrrole MoietyBoryana Borisova0Stanislava Vladimirova1Hristina Nocheva2Marie Laronze-Cochard3Stéphane Gérard4Stoyko Petrin5Dancho Danalev6Biotechnology Department, University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd, 1756 Sofia, BulgariaOrganic Synthesis Department, University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd, 1756 Sofia, BulgariaDepartment of Physiology and Pathophysiology, Faculty of Medicine, Medical University-Sofia, Sv. Georgi Sofiyski Blvd 1, 1431 Sofia, BulgariaInstitut de Chimie Moléculaire de Reims (ICMR)—UMR CNRS 7312, Université de Reims Champagne-Ardenne, UFR Pharmacie, 51 rue Cognacq-Jay, 51100 Reims, FranceInstitut de Chimie Moléculaire de Reims (ICMR)—UMR CNRS 7312, Université de Reims Champagne-Ardenne, UFR Pharmacie, 51 rue Cognacq-Jay, 51100 Reims, FranceBiotechnology Department, University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd, 1756 Sofia, BulgariaBiotechnology Department, University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd, 1756 Sofia, BulgariaBackground: Bioconjugates are promising alternatives for the multiple targeting of any disease. Pyrrole heterocycle is well known with many activities and is a building block of a lot of medical drugs. On the other hand, peptides are short molecules with many advantages such as small size, ability to penetrate the cell membrane and bond-specific receptors, vectorizing potential, etc. Thus, hybrid molecules between peptide and pyrrole moiety could be a promising alternative as an anti-pain tool. Methods: New bioconjugates with a general formula Pyrrole (α-/β-acid)-FELL-OH (NH<sub>2</sub>) were synthesized using Fmoc/OtBu peptide synthesis on solid support. HPLC was used to monitor the purity of newly synthesized bioconjugates. Their structures were proven by electrospray ionization mass spectrometry. The Paw Pressure test (Randall–Selitto test) was used to examinate the analgesic activity. Hydrolytic stability of targeted structures was monitored in three model systems with pH 2.0, 7.4 and 9.0, including specific enzymes by means of the HPLC-UV method. Results: The obtained results reveal that all newly synthesized bioconjugates have analgesic activity according to the used test but free pyrrole acids have the best analgesic activity. Conclusions: Although free pyrrole acids showed the best analgesic activity, they are the most unstable for hydrolysis. Combination with peptide structure leads to the hydrolytic stabilization of the bioconjugates, albeit with slightly reduced activity.https://www.mdpi.com/2227-9059/11/12/3265bioconguatesFELLpyrrolepeptidesanalgesic activityhydrolytic stability |
| spellingShingle | Boryana Borisova Stanislava Vladimirova Hristina Nocheva Marie Laronze-Cochard Stéphane Gérard Stoyko Petrin Dancho Danalev Synthesis, Hydrolytic Stability and In Vivo Biological Study of Bioconjugates of the Tetrapeptides FELL Containing Pyrrole Moiety Biomedicines bioconguates FELL pyrrole peptides analgesic activity hydrolytic stability |
| title | Synthesis, Hydrolytic Stability and In Vivo Biological Study of Bioconjugates of the Tetrapeptides FELL Containing Pyrrole Moiety |
| title_full | Synthesis, Hydrolytic Stability and In Vivo Biological Study of Bioconjugates of the Tetrapeptides FELL Containing Pyrrole Moiety |
| title_fullStr | Synthesis, Hydrolytic Stability and In Vivo Biological Study of Bioconjugates of the Tetrapeptides FELL Containing Pyrrole Moiety |
| title_full_unstemmed | Synthesis, Hydrolytic Stability and In Vivo Biological Study of Bioconjugates of the Tetrapeptides FELL Containing Pyrrole Moiety |
| title_short | Synthesis, Hydrolytic Stability and In Vivo Biological Study of Bioconjugates of the Tetrapeptides FELL Containing Pyrrole Moiety |
| title_sort | synthesis hydrolytic stability and in vivo biological study of bioconjugates of the tetrapeptides fell containing pyrrole moiety |
| topic | bioconguates FELL pyrrole peptides analgesic activity hydrolytic stability |
| url | https://www.mdpi.com/2227-9059/11/12/3265 |
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