Optimization of a nicotine degrading enzyme for potential use in treatment of nicotine addiction.

ABSTRACT:

Background

Smoking and tobacco use continue to be the largest preventable causes of death globally. A novel therapeutic approach has recently been proposed: administration of an enzyme that degrades nicotine, the main addictive component of tobacco, minimizing brain exposure and reducing its reinforcing effects. Pre-clinical proof of concept has been previously established through dosing the amine oxidase NicA2 from Pseudomonas putida in rat nicotine self-administration models of addiction.

Results

This paper describes efforts towards optimizing NicA2 for potential therapeutic use: enhancing potency, improving its pharmacokinetic profile, and attenuating immunogenicity. Libraries randomizing residues located in all 22 active site positions of NicA2 were screened. 58 single m

SUBMITTER: Thisted T 

PROVIDER: S-EPMC6679477 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature