An immobilized acetylcholinesterase as test system to screen new inhibitor drugs to treat Alzheimer's disease

Autor(es)

Lopes Vilela, Adriana Ferreira ^{[1, 2]} ; Cardoso, Carmen Lucia ^[2] ; Mateo, Cesar ^[1]

Afiliação do(s) autor(es)

^[1] CSIC, Inst Catalisis & Petroleoquim, Dept Biocatalisis, Marie Curie 2, Campus UAM, Madrid 28049 - Spain

^[2] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Grp Cromatog Bioafinidade & Prod Nat, Dept Quim, BR-1404090 Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SENSORS AND ACTUATORS B-CHEMICAL; v. 278, p. 196-201, JAN 1 2019.
• Citações Web of Science: 2

Resumo

This study presents a rapid and simple method to screen and detect new drugs to treat Alzheimer's disease. The method uses a test system based on an immobilized acetylcholinesterase from Electrophorus electricus (AChE). The optimal AChE immobilized preparation retained 65% of the original catalytic activity; immobilization improved AChE stability by approximately 200-fold. Inhibition and usability of immobilized AChE in real conditions was studied using tacrine as model inhibitor. The immobilized system enabled to determine variables like IC50, K-i, K-D, and Delta G(o') in an uncomplicated way and proved to be an interesting tool for rapid screening of the ability of new target compounds to inhibit AChE. System inertia was also studied to avoid false positives. The system was optimized by making the un-specific interactions between AChE and other compounds from a vegetable extract negligible. Optimization of the immobilized AChE system allowed its efficient application to test mixtures of tacrine, a standard inhibitor, and vegetable extracts as AChE inhibitors. The system was reused at least 15 times with minimal AChE activity loss. (AU)

• Processo FAPESP: 16/15037-5 - Co-imobilização das enzimas acetilcolinesterase e beta-secretase 1: estudo de condições para triagem de ligantes
• Beneficiário: Adriana Ferreira Lopes Vilela
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 13/01710-1 - Ligantes enzimáticos: novos modelos de triagem
• Beneficiário: Quezia Bezerra Cass
• Modalidade de apoio: Auxílio à Pesquisa - Temático