Identification and characterization of aptameric inhibitors of human neutrophil elastase.
Humans
Cystic Fibrosis
/ drug therapy
Emphysema
/ drug therapy
Leukocyte Elastase
/ antagonists & inhibitors
Neutrophils
/ drug effects
Serine Proteinase Inhibitors
/ chemical synthesis
Aptamers, Nucleotide
/ chemical synthesis
Sensitivity and Specificity
Enzyme Activation
/ drug effects
Proteolysis
/ drug effects
Cells, Cultured
aptamer
elastase
human neutrophil elastase
neutrophil
pulmonary disease
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
24
10
2022
revised:
17
05
2023
accepted:
01
06
2023
medline:
31
8
2023
pubmed:
8
6
2023
entrez:
7
6
2023
Statut:
ppublish
Résumé
Human neutrophil elastase (HNE) plays a pivotal role in innate immunity, inflammation, and tissue remodeling. Aberrant proteolytic activity of HNE contributes to organ destruction in various chronic inflammatory diseases including emphysema, asthma, and cystic fibrosis. Therefore, elastase inhibitors could alleviate the progression of these disorders. Here, we used the systematic evolution of ligands by exponential enrichment to develop ssDNA aptamers that specifically target HNE. We determined the specificity of the designed inhibitors and their inhibitory efficacy against HNE using biochemical and in vitro methods, including an assay of neutrophil activity. Our aptamers inhibit the elastinolytic activity of HNE with nanomolar potency and are highly specific for HNE and do not target other tested human proteases. As such, this study provides lead compounds suitable for the evaluation of their tissue-protective potential in animal models.
Identifiants
pubmed: 37286041
pii: S0021-9258(23)01917-8
doi: 10.1016/j.jbc.2023.104889
pmc: PMC10359491
pii:
doi:
Substances chimiques
Leukocyte Elastase
EC 3.4.21.37
Serine Proteinase Inhibitors
0
Aptamers, Nucleotide
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104889Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.