Chem. Commun.: nicotine degrading enzyme can help smokers quit smoking

It's hard to quit smoking According to a 2011 U.S government report, almost 70% of smokers want to quit smoking, and more than half of smokers have started to quit smoking, but less than 6% of them succeed At present, the success rate of smoking cessation treatment and prescription drugs to help people quit smoking is different Smoking is the main cause of preventable diseases in the world Effective smoking cessation aids are essential to reduce the prevalence of smoking and related diseases Pharmacokinetic data of nica2 and nica2-j1in rat serum (source: chem Commin.) due to the low success rate of "pharmacodynamic" treatment strategy, there has been a method called "pharmacokinetic" to treat drug addiction in the past decade Among them, immunopharmacotherapy prepares vaccines to stimulate the production of specific antibodies Many drugs of abuse have been targeted, including cocaine, methamphetamine, heroin and nicotine The general idea of immunopharmacotherapy is that the complex size of antibody and drug combination is too large to pass through the blood-brain barrier, which reduces the concentration / speed of drug entering the brain, and finally deactivates the drug addiction Unfortunately, the vaccine that has been tested in clinical trials to block nicotine addiction fails to achieve the main goal of increasing the withdrawal rate compared with placebo A number of clinical studies have shown that cigarettes with low nicotine content lead to reduced nicotine intake, increased abstinence rate and recurrence time Therefore, the pharmacokinetic method of nicotine addiction treatment may still have a significant impact on human health, but it is necessary to have sufficient pharmacokinetic ability to significantly reduce the concentration of free drugs The effect of nica2-j1on nicotine withdrawal rats (source: chem Commin.) was compared with the simple idea of preventing nicotine from entering the brain through antibody binding Another strategy to reduce the brain concentration of nicotine was to degrade it By decomposing nicotine to reduce its peripheral circulation, the effective concentration of nicotine in brain can be reduced As early as 2015, Kim D Janda of Scripps Research Institute and his colleagues reported that Pseudomonas putida has an enzyme nica2, which can catalyze the oxidation of nicotine to N-methyl tyrosine When the enzyme is tested in vitro, a very valuable test result is found, but when it is transferred to the in vivo experiment, the kidney will expel nica2, making the concentration of this enzyme in vivo difficult to maintain in the effective range After 1 / 5 / 7 day of administration of nica2-j1nicotine concentrations in the blood (a) and brain (b) of rats (source: chem Commun.) Janda and his team now have stable nica2 derivatives (nica2-j1s) The first 52 amino acids of nica2 were not involved in its activity, so the team removed 50 of them and bound the remaining enzyme to albumin Binding nica2 to albumin, the most abundant protein in the plasma, increases its half-life in the body They used rats to test the new treatment The rats treated with modified enzyme were not addicted to nicotine, and the withdrawal symptoms were less than those in the control group Moreover, the enzyme can completely remove nicotine from rat blood and decompose it into harmless and metabolizable non psychoactive substances This new approach proves the possibility of biological products in the treatment of drug abuse Janda said they would continue to optimize the system to improve stability in the body and eliminate potential risks that could lead to an immune response Paper link: http://pubs.rsc.org/en/content/articlelanding/2018/cc/c7cc09134f correspondence Author: Kim D Janda http:// Name = Janda