Synthesis, In Silico Log<em>p</em> Study, and In Vivo Analgesic Activity of Analogs of Tetrapeptide FELL
Background: The inflammatory process represents a specific response of the organism’s immune system. More often, it is related to the rising pain in the affected area. Independently of its origin, pain represents a complex and multidimensional acute or chronic subjective unpleasant perception. Curre...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/8/1183 |
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| author | Boryana Borisova Hristina Nocheva Stéphane Gérard Marie Laronze-Cochard Stefan Dobrev Silvia Angelova Stoyko Petrin Dancho Danalev |
| author_facet | Boryana Borisova Hristina Nocheva Stéphane Gérard Marie Laronze-Cochard Stefan Dobrev Silvia Angelova Stoyko Petrin Dancho Danalev |
| author_sort | Boryana Borisova |
| collection | DOAJ |
| description | Background: The inflammatory process represents a specific response of the organism’s immune system. More often, it is related to the rising pain in the affected area. Independently of its origin, pain represents a complex and multidimensional acute or chronic subjective unpleasant perception. Currently, medical doctors prescribe various analgesics for pain treatment, but unfortunately, many of them have adverse effects or are not strong enough to suppress the pain. Thus, the search for new pain-relieving medical drugs continues. Methods: New tetrapeptide analogs of FELL with a generaanalgesic-Glu-X<sup>3</sup>-X<sup>4</sup>-Z, where X = Nle, Ile, or Val and Z = NH<sub>2</sub> or COOH, containing different hydrophobic amino acids at positions 3 and 4, were synthesized by means of standard solid-phase peptide synthesis using the Fmoc/OtBu strategy in order to study the influence of structure and hydrophobicity on the analgesic activity. The purity of all compounds was monitored by HPLC, and their structures were proven by ESI-MS. Log<i>p</i> values (partition coefficient in octanol/water) for FELL analogs were calculated. Analgesic activity was examined by the Paw-pressure test (Randall-Selitto test). Results: The obtained results reveal that Leu is the best choice as a hydrophobic amino acid in the FELL structure. Conclusions: The best analgesic activity is found in the parent compound FELL and its C-terminal amide analog. |
| first_indexed | 2024-03-10T23:39:34Z |
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| id | doaj.art-6ec7a4ec312449d290621bd351b70cac |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T23:39:34Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-6ec7a4ec312449d290621bd351b70cac2023-11-19T02:35:19ZengMDPI AGPharmaceuticals1424-82472023-08-01168118310.3390/ph16081183Synthesis, In Silico Log<em>p</em> Study, and In Vivo Analgesic Activity of Analogs of Tetrapeptide FELLBoryana Borisova0Hristina Nocheva1Stéphane Gérard2Marie Laronze-Cochard3Stefan Dobrev4Silvia Angelova5Stoyko Petrin6Dancho Danalev7Biotechnology Department, University of Chemical Technology and Metallurgy, 8 Kliment Ohridski Blvd., 1756 Sofia, BulgariaDepartment of Physiology and Pathophysiology, Faculty of Medicine, Medical University of 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, 51096 Reims, FranceInstitut de Chimie Moléculaire de Reims (ICMR)-UMR CNRS 7312, Université de Reims Champagne-Ardenne, UFR Pharmacie, 51 Rue Cognacq-Jay, 51096 Reims, FranceInstitute of Optical Materials and Technologies “Acad. J. Malinowski”, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 109, 1113 Sofia, BulgariaInstitute of Optical Materials and Technologies “Acad. J. Malinowski”, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 109, 1113 Sofia, BulgariaBiotechnology 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: The inflammatory process represents a specific response of the organism’s immune system. More often, it is related to the rising pain in the affected area. Independently of its origin, pain represents a complex and multidimensional acute or chronic subjective unpleasant perception. Currently, medical doctors prescribe various analgesics for pain treatment, but unfortunately, many of them have adverse effects or are not strong enough to suppress the pain. Thus, the search for new pain-relieving medical drugs continues. Methods: New tetrapeptide analogs of FELL with a generaanalgesic-Glu-X<sup>3</sup>-X<sup>4</sup>-Z, where X = Nle, Ile, or Val and Z = NH<sub>2</sub> or COOH, containing different hydrophobic amino acids at positions 3 and 4, were synthesized by means of standard solid-phase peptide synthesis using the Fmoc/OtBu strategy in order to study the influence of structure and hydrophobicity on the analgesic activity. The purity of all compounds was monitored by HPLC, and their structures were proven by ESI-MS. Log<i>p</i> values (partition coefficient in octanol/water) for FELL analogs were calculated. Analgesic activity was examined by the Paw-pressure test (Randall-Selitto test). Results: The obtained results reveal that Leu is the best choice as a hydrophobic amino acid in the FELL structure. Conclusions: The best analgesic activity is found in the parent compound FELL and its C-terminal amide analog.https://www.mdpi.com/1424-8247/16/8/1183FELL analogsanalgesic activitypeptide synthesispaw-pressure test |
| spellingShingle | Boryana Borisova Hristina Nocheva Stéphane Gérard Marie Laronze-Cochard Stefan Dobrev Silvia Angelova Stoyko Petrin Dancho Danalev Synthesis, In Silico Log<em>p</em> Study, and In Vivo Analgesic Activity of Analogs of Tetrapeptide FELL Pharmaceuticals FELL analogs analgesic activity peptide synthesis paw-pressure test |
| title | Synthesis, In Silico Log<em>p</em> Study, and In Vivo Analgesic Activity of Analogs of Tetrapeptide FELL |
| title_full | Synthesis, In Silico Log<em>p</em> Study, and In Vivo Analgesic Activity of Analogs of Tetrapeptide FELL |
| title_fullStr | Synthesis, In Silico Log<em>p</em> Study, and In Vivo Analgesic Activity of Analogs of Tetrapeptide FELL |
| title_full_unstemmed | Synthesis, In Silico Log<em>p</em> Study, and In Vivo Analgesic Activity of Analogs of Tetrapeptide FELL |
| title_short | Synthesis, In Silico Log<em>p</em> Study, and In Vivo Analgesic Activity of Analogs of Tetrapeptide FELL |
| title_sort | synthesis in silico log em p em study and in vivo analgesic activity of analogs of tetrapeptide fell |
| topic | FELL analogs analgesic activity peptide synthesis paw-pressure test |
| url | https://www.mdpi.com/1424-8247/16/8/1183 |
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