Improvements on a chemically contiguous hapten for a vaccine to address fentanyl-contaminated heroin.


Journal

Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298

Informations de publication

Date de publication:
01 07 2021
Historique:
received: 23 04 2021
revised: 13 05 2021
accepted: 18 05 2021
pubmed: 26 5 2021
medline: 9 11 2021
entrez: 25 5 2021
Statut: ppublish

Résumé

Unintentional overdose deaths related to opioids and psychostimulants have increased in prevalence due to the adulteration of these drugs with fentanyl. Synergistic effects between illicit compounds and fentanyl cause aggravated respiratory depression, leading to inadvertent fatalities. Traditional small-molecule therapies implemented in the expanding opioid epidemic present numerous problems since they interact with the same opioid receptors in the brain as the abused drugs. In this study, we report an optimized dual hapten for use as an immunopharmacotherapeutic tool in order to develop antibodies capable of binding to fentanyl-contaminated heroin in the periphery, thus impeding the drugs' psychoactive effects on the central nervous system. This vaccine produced antibodies with nanomolar affinities and effectively blocked opioid analgesic effects elicited by adulterated heroin. These findings provide further insight into the development of chemically contiguous haptens for broad-spectrum immunopharmacotherapies against opioid use disorders.

Identifiants

pubmed: 34034147
pii: S0968-0896(21)00233-9
doi: 10.1016/j.bmc.2021.116225
pii:
doi:

Substances chimiques

Haptens 0
Vaccines 0
Heroin 70D95007SX
Fentanyl UF599785JZ

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

116225

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

Auteurs

Hyeri Park (H)

Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States.

Jinny Claire Lee (JC)

Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States.

Lisa M Eubanks (LM)

Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States.

Beverly Ellis (B)

Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States.

Bin Zhou (B)

Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States.

Kim D Janda (KD)

Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States. Electronic address: kdjanda@scripps.edu.

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Classifications MeSH