C-terminal tails mimicking bioactive intermediates cause different plasma degradation patterns and kinetics in neuropeptides γ-MSH, α-MSH, and neurotensin.

Détails

ID Serval
serval:BIB_D2B087BDB61E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
C-terminal tails mimicking bioactive intermediates cause different plasma degradation patterns and kinetics in neuropeptides γ-MSH, α-MSH, and neurotensin.
Périodique
Journal of peptide science
Auteur⸱e⸱s
Palazzi L., Pasquato A., Vicario M., Roulin A., Polverino de Laureto P., Cendron L.
ISSN
1099-1387 (Electronic)
ISSN-L
1075-2617
Statut éditorial
Publié
Date de publication
11/2020
Peer-reviewed
Oui
Volume
26
Numéro
11
Pages
e3279
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Peptides are attractive drugs because of their specificity and minimal off-target effects. Short half-lives are within their major drawbacks, limiting actual use in clinics. The golden standard in therapeutic peptide development implies identification of a minimal core sequence, then modified to increase stability through several strategies, including the introduction of nonnatural amino acids, cyclization, and lipidation. Here, we investigated plasma degradations of hormone sequences all composed of a minimal active core peptide and a C-terminal extension. We first investigated pro-opimelanocortin (POMC) γ2/γ3-MSH hormone behavior and extended our analysis to POMC-derived α-melanocyte stimulating hormone/adrenocorticotropic hormone signaling neuropeptides and neurotensin. We demonstrated that in all the three cases analyzed in this study, few additional residues mimicking the natural sequence alter both peptide stability and the mechanism(s) of degradation of the minimal conserved functional pattern. Our results suggest that the impact of extensions on the bioactivity of a peptide drug has to be carefully evaluated throughout the optimization process.
Mots-clé
drug optimization, in serum stability, melanocyte stimulating hormones, peptide half-life, peptide hormones, pro-opiomelanocortin hormone, proteolysis
Pubmed
Web of science
Création de la notice
03/09/2020 12:34
Dernière modification de la notice
24/10/2020 6:21
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