Vaccine design through transition state mimicry of heroin hydrolysis. (11th May 2021)

• Record Type: Journal Article
• Authors: Belz, Tyson F.; Lin, Mingliang; Eubanks, Lisa M.; Ellis, Beverly; Janda, Kim D.
• Is Part Of: Tetrahedron letters. Volume 71(2021)
• Publication Date: 2021-05-11
• Subjects: Heroin hydrolysis -- Antibody catalysis -- Transition state mimic -- Vaccine -- Increased drug metabolism; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2021.153045
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: Vaccination against opioids as a means to treat substance abuse. Antibody catalysis to increase heroin's metabolism. Antinociception and blood brain barrier analysis of vaccines efficacy. Transition-state haptens for generating catalytic antibodies against heroin. Abstract: A transition state mimic, heroin 3, 6-diphosphonate ester (H2P ), was synthesized and the KLH-hapten immunoconjugate was administered to rodents to assess its ability to generate a catalytic antibody response. The antibody titers elicited by the H2P vaccine were measured and compared to a vaccine comprised of a non-transition state hapten. Biodistribution and kinetic studies revealed the presence of high morphine levels in the blood due to antibody catalysis in the H2P vaccinated animals, while also exhibiting significance in behavioral assays. Our results indicate heroin drug metabolism was perturbed via antibody catalysis providing a starting point for developing monoclonal catalytic antibodies against heroin.