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Synthesis, In Silico Logp Study, and In Vitro 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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Autores principales: Borisova, Boryana, Nocheva, Hristina, Gérard, Stéphane, Laronze-Cochard, Marie, Dobrev, Stefan, Angelova, Silvia, Petrin, Stoyko, Danalev, Dancho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10458596/
https://www.ncbi.nlm.nih.gov/pubmed/37631098
http://dx.doi.org/10.3390/ph16081183
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author Borisova, Boryana
Nocheva, Hristina
Gérard, Stéphane
Laronze-Cochard, Marie
Dobrev, Stefan
Angelova, Silvia
Petrin, Stoyko
Danalev, Dancho
author_facet Borisova, Boryana
Nocheva, Hristina
Gérard, Stéphane
Laronze-Cochard, Marie
Dobrev, Stefan
Angelova, Silvia
Petrin, Stoyko
Danalev, Dancho
author_sort Borisova, Boryana
collection PubMed
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(3)-X(4)-Z, where X = Nle, Ile, or Val and Z = NH(2) 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. Logp 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.
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spelling pubmed-104585962023-08-27 Synthesis, In Silico Logp Study, and In Vitro Analgesic Activity of Analogs of Tetrapeptide FELL Borisova, Boryana Nocheva, Hristina Gérard, Stéphane Laronze-Cochard, Marie Dobrev, Stefan Angelova, Silvia Petrin, Stoyko Danalev, Dancho Pharmaceuticals (Basel) Article 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(3)-X(4)-Z, where X = Nle, Ile, or Val and Z = NH(2) 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. Logp 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. MDPI 2023-08-21 /pmc/articles/PMC10458596/ /pubmed/37631098 http://dx.doi.org/10.3390/ph16081183 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Borisova, Boryana
Nocheva, Hristina
Gérard, Stéphane
Laronze-Cochard, Marie
Dobrev, Stefan
Angelova, Silvia
Petrin, Stoyko
Danalev, Dancho
Synthesis, In Silico Logp Study, and In Vitro Analgesic Activity of Analogs of Tetrapeptide FELL
title Synthesis, In Silico Logp Study, and In Vitro Analgesic Activity of Analogs of Tetrapeptide FELL
title_full Synthesis, In Silico Logp Study, and In Vitro Analgesic Activity of Analogs of Tetrapeptide FELL
title_fullStr Synthesis, In Silico Logp Study, and In Vitro Analgesic Activity of Analogs of Tetrapeptide FELL
title_full_unstemmed Synthesis, In Silico Logp Study, and In Vitro Analgesic Activity of Analogs of Tetrapeptide FELL
title_short Synthesis, In Silico Logp Study, and In Vitro Analgesic Activity of Analogs of Tetrapeptide FELL
title_sort synthesis, in silico logp study, and in vitro analgesic activity of analogs of tetrapeptide fell
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10458596/
https://www.ncbi.nlm.nih.gov/pubmed/37631098
http://dx.doi.org/10.3390/ph16081183
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