Structure-Based Design of Glycosylated Oxytocin Analogues with Improved Selectivity and Antinociceptive Activity.
Journal
ACS medicinal chemistry letters
ISSN: 1948-5875
Titre abrégé: ACS Med Chem Lett
Pays: United States
ID NLM: 101521073
Informations de publication
Date de publication:
09 Feb 2023
09 Feb 2023
Historique:
received:
24
10
2022
accepted:
20
01
2023
pmc-release:
09
02
2024
entrez:
16
2
2023
pubmed:
17
2
2023
medline:
17
2
2023
Statut:
epublish
Résumé
Acute and chronic pain is often treated with opioids despite the negative side effects of constipation, physical dependence, respiratory depression, and overdose. The misuse of opioid analgesics has given rise to the opioid crisis/epidemic, and alternate nonaddictive analgesics are urgently needed. Oxytocin, a pituitary hormone, is an alternative to the small molecule treatments available and has been used as an analgesic as well as for the treatment and prevention of opioid use disorder (OUD). Clinical implementation is limited by its poor pharmacokinetic profile, a result of the labile disulfide bond between two cysteine residues in the native sequence. Stable brain penetrant oxytocin analogues have been synthesized by replacement of the disulfide bond with a stable lactam and glycosidation of the C-terminus. These analogues show exquisite selectivity for the oxytocin receptor and potent
Identifiants
pubmed: 36793431
doi: 10.1021/acsmedchemlett.2c00455
pmc: PMC9923833
doi:
Types de publication
Journal Article
Langues
eng
Pagination
163-170Informations de copyright
© 2023 American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare the following competing financial interest(s): J.M.S., M.L.H., T.F., and R.P. are co-founders of Teleport Pharmaceuticals, LLC, a company for the development and commercialization of glycosylated peptides for neurodegenerative disease and other neurological conditions. J.M.S. is an equity holder in Botanical Results, LLC, a local cannabidiol company; no company products or interests were tested here.
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