Insightful Backbone Modifications Preventing Proteolytic Degradation of Neurotensin Analogs Improve NT
NTS1
hypothermia
proteolytic stability
reduced peptide bonds
unnatural amino acids
Journal
Frontiers in chemistry
ISSN: 2296-2646
Titre abrégé: Front Chem
Pays: Switzerland
ID NLM: 101627988
Informations de publication
Date de publication:
2020
2020
Historique:
received:
10
03
2020
accepted:
17
04
2020
entrez:
26
6
2020
pubmed:
26
6
2020
medline:
26
6
2020
Statut:
epublish
Résumé
Therapeutic hypothermia represents a brain-protective strategy for multiple emergency situations, such as stroke or traumatic injury. Neurotensin (NT), which exerts its effects through activation of two G protein-coupled receptors, namely NTS1 and NTS2, induces a strong and long-lasting decrease in core body temperature after its central administration. Growing evidence demonstrates that NTS1 is the receptor subtype mediating the hypothermic action of NT. As such, potent NTS1 agonists designed on the basis of the minimal C-terminal NT(8-13) bioactive fragment have been shown to produce mild hypothermia and exert neuroprotective effects under various clinically relevant conditions. The high susceptibility of NT(8-13) to protease degradation (half-life <2 min) represents, however, a serious limitation for its use in pharmacological therapy. In light of this, we report here a structure-activity relationship study in which pairs of NT(8-13) analogs have been developed, based on the incorporation of a reduced Lys
Identifiants
pubmed: 32582624
doi: 10.3389/fchem.2020.00406
pmc: PMC7291367
doi:
Types de publication
Journal Article
Langues
eng
Pagination
406Informations de copyright
Copyright © 2020 Previti, Vivancos, Rémond, Beaulieu, Longpré, Ballet, Sarret and Cavelier.
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