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Kinetic studies of novel inhibitors of endomorphin degrading enzymes
Endomorphins (EMs), two endogenous μ-opioid receptor selective ligands, are attractive lead compounds for opioid-based pain management studies. However, these peptides are quickly degraded by peptidases, in particular by dipeptidylpeptidase IV (DPP IV) and aminopeptidase M (APM). Targeting enzymatic...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer-Verlag
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359464/ https://www.ncbi.nlm.nih.gov/pubmed/22707871 http://dx.doi.org/10.1007/s00044-011-9666-5 |
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author | Perlikowska, Renata Fichna, Jakub do-Rego, Jean Claude Gach, Katarzyna Janecka, Anna |
author_facet | Perlikowska, Renata Fichna, Jakub do-Rego, Jean Claude Gach, Katarzyna Janecka, Anna |
author_sort | Perlikowska, Renata |
collection | PubMed |
description | Endomorphins (EMs), two endogenous μ-opioid receptor selective ligands, are attractive lead compounds for opioid-based pain management studies. However, these peptides are quickly degraded by peptidases, in particular by dipeptidylpeptidase IV (DPP IV) and aminopeptidase M (APM). Targeting enzymatic degradation is one approach to prolong endomorphin activity. In this study we characterized the action of two new inhibitors of similar to endomorphins structure, Tyr-Pro-Ala-NH(2) (EMDB-2) and Tyr-Pro-Ala-OH (EMDB-3), which were designed earlier in our laboratory. The presented data give evidence that EMDB-2 and EMDB-3 are potent inhibitors of enzymes responsible for endomorphin cleavage. These compounds are stable and easily synthesized. EMDB-2 and EMDB-3 are competitive inhibitors of both, DPP IV and APM, with K (i) values in micromolar range. They are less potent than diprotin A in protecting EMs against DPP IV but more potent than actinonin in protecting these peptides against APM. |
format | Online Article Text |
id | pubmed-3359464 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Springer-Verlag |
record_format | MEDLINE/PubMed |
spelling | pubmed-33594642012-06-13 Kinetic studies of novel inhibitors of endomorphin degrading enzymes Perlikowska, Renata Fichna, Jakub do-Rego, Jean Claude Gach, Katarzyna Janecka, Anna Med Chem Res Original Research Endomorphins (EMs), two endogenous μ-opioid receptor selective ligands, are attractive lead compounds for opioid-based pain management studies. However, these peptides are quickly degraded by peptidases, in particular by dipeptidylpeptidase IV (DPP IV) and aminopeptidase M (APM). Targeting enzymatic degradation is one approach to prolong endomorphin activity. In this study we characterized the action of two new inhibitors of similar to endomorphins structure, Tyr-Pro-Ala-NH(2) (EMDB-2) and Tyr-Pro-Ala-OH (EMDB-3), which were designed earlier in our laboratory. The presented data give evidence that EMDB-2 and EMDB-3 are potent inhibitors of enzymes responsible for endomorphin cleavage. These compounds are stable and easily synthesized. EMDB-2 and EMDB-3 are competitive inhibitors of both, DPP IV and APM, with K (i) values in micromolar range. They are less potent than diprotin A in protecting EMs against DPP IV but more potent than actinonin in protecting these peptides against APM. Springer-Verlag 2011-05-20 2012 /pmc/articles/PMC3359464/ /pubmed/22707871 http://dx.doi.org/10.1007/s00044-011-9666-5 Text en © The Author(s) 2011 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. |
spellingShingle | Original Research Perlikowska, Renata Fichna, Jakub do-Rego, Jean Claude Gach, Katarzyna Janecka, Anna Kinetic studies of novel inhibitors of endomorphin degrading enzymes |
title | Kinetic studies of novel inhibitors of endomorphin degrading enzymes |
title_full | Kinetic studies of novel inhibitors of endomorphin degrading enzymes |
title_fullStr | Kinetic studies of novel inhibitors of endomorphin degrading enzymes |
title_full_unstemmed | Kinetic studies of novel inhibitors of endomorphin degrading enzymes |
title_short | Kinetic studies of novel inhibitors of endomorphin degrading enzymes |
title_sort | kinetic studies of novel inhibitors of endomorphin degrading enzymes |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359464/ https://www.ncbi.nlm.nih.gov/pubmed/22707871 http://dx.doi.org/10.1007/s00044-011-9666-5 |
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