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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...

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Autores principales: Perlikowska, Renata, Fichna, Jakub, do-Rego, Jean Claude, Gach, Katarzyna, Janecka, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer-Verlag 2011
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.
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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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