77001-77-5Relevant academic research and scientific papers
Synthesis and biological evaluation of a lipopeptide-based methamphetamine vaccine
Liao, Fan,Wang, Hanxuan,Dao, Yuankun,Yuan, Kai,Lu, Jiazhen,Shi, Jie,Han, Ying,Dong, Suwei,Lu, Lin
supporting information, p. 1577 - 1581 (2020/11/13)
We describe an application of carrier protein-free strategy in constructing a fully synthetic methamphetamine (METH) vaccine that contains three components: Toll-like receptor 2 ligand, Th2 epitope, and METH hapten. The immunological evaluation in mice revealed high titers of METH-specific antibodies induced by the construct and the activation of humoral immunity that would be beneficial for neutralization and clearance of the METH molecule. Behavioral experiments indicated that the synthetic vaccine attenuated the acquisition of METH-induced conditioned place preference and inhibited the initiation and expression of METH-induced locomotor sensitization. These results demonstrate that the lipopeptide-based vaccine has invoked an immune response and showed the potential of preventing the rewarding and psychoactive effects of METH.
Impact of distinct chemical structures for the development of a methamphetamine vaccine
Moreno, Amira Y.,Mayorov, Alexander V.,Janda, Kim D.
supporting information; experimental part, p. 6587 - 6595 (2011/06/27)
(+)-Methamphetamine (METH) use and addiction has grown at alarming rates over the past two decades, while no approved pharmacotherapy exists for its treatment. Immunopharmacotherapy has the potential to offer relief through producing highly specific antibodies that prevent drug penetration across the blood-brain barrier thus decreasing reinforcement of the behavior. Current immunotherapy efforts against methamphetamine have focused on a single hapten structure, namely linker attachment at the aromatic ring of the METH molecule. Hapten design is largely responsible for immune recognition, as it affects presentation of the target antigen and thus the quality of the response. In the current paper we report the systematic generation of a series of haptens designed to target the most stable conformations of methamphetamine as determined by molecular modeling. On the basis of our previous studies with nicotine, we show that introduction of strategic molecular constraint is able to maximize immune recognition of the target structure as evidenced by higher antibody affinity. Vaccination of GIX+ mice with six unique METH immunoconjugates resulted in high antibody titers for three particularly promising formulations (45-108 μg/mL, after the second immunization) and high affinity (82, 130, and 169 nM for MH2, MH6, and MH7 hapten-based vaccines, respectively). These findings represent a unique approach to the design of new vaccines against methamphetamine abuse.
