Journal of advanced research · 2021
Calix[n]arene-based immunogens: A new non-proteic strategy for anti-cocaine vaccine.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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da Silva Neto Leonardo, da Silva Maia Angélica Faleiros, Godin Adriana Martins, de Almeida Augusto Paulo Sérgio, Pereira Raissa Lima Gonçalves, Caligiorne Sordaini Maria, Alves Rosemeire Brondi, Fernandes Simone Odília Antunes, Cardoso Valbert Nascimento, Goulart Gisele Assis Castro, Martins Felipe Terra, das Neves Maila de Castro Lourenço, Garcia Frederico Duarte, de Fátima Ângelo
Аннотация
INTRODUCTION: Cocaine use disorder is a significant public health issue without a current specific approved treatment. Among different approaches to this disorder, it is possible to highlight a promising immunologic strategy in which an immunogenic agent may reduce the reinforcing effects of the drug if they are able to yield sufficient specific antibodies capable to bind cocaine and/or its psychoactive metabolites before entering into the brain. Several carriers have been investigated in the anti-cocaine vaccine development; however, they generally present a very complex chemical structure, which potentially hampers the proper assessment of the coupling efficiency between the hapten units and the protein structure.
OBJECTIVES: The present study reports the design, synthesis and preclinical evaluation of two novel calix[n]arene-based anti-cocaine immunogens (herein named as V4N2 and V8N2) by the tethering of the hydrolysis-tolerant hapten GNE (15) on calix[4]arene and calix[8]arene moieties.
METHODS: The preclinical assessment corresponded to the immunogenicity and dose-response evaluation of V4N2 and V8N2. The potential of the produced antibodies to reduce the passage of cocaine analogue through the blood-brain-barrier (BBB), modifying its biodistribution was also investigated.
RESULTS: Both calix[n]arene-based immunogens elicited high titers of cocaine antibodies that modified the biodistribution of a cocaine radiolabeled analogue (99mTc-TRODAT-1) and decreased cocaine-induced behavior, according to an animal model.
CONCLUSION: The present results demonstrate the potential of V4N2 and V8N2 as immunogens for the treatment of cocaine use disorder.
OBJECTIVES: The present study reports the design, synthesis and preclinical evaluation of two novel calix[n]arene-based anti-cocaine immunogens (herein named as V4N2 and V8N2) by the tethering of the hydrolysis-tolerant hapten GNE (15) on calix[4]arene and calix[8]arene moieties.
METHODS: The preclinical assessment corresponded to the immunogenicity and dose-response evaluation of V4N2 and V8N2. The potential of the produced antibodies to reduce the passage of cocaine analogue through the blood-brain-barrier (BBB), modifying its biodistribution was also investigated.
RESULTS: Both calix[n]arene-based immunogens elicited high titers of cocaine antibodies that modified the biodistribution of a cocaine radiolabeled analogue (99mTc-TRODAT-1) and decreased cocaine-induced behavior, according to an animal model.
CONCLUSION: The present results demonstrate the potential of V4N2 and V8N2 as immunogens for the treatment of cocaine use disorder.