A computer-generated plan to develop an intelligent biosensor for investigation of the inhibition of renin by aliskiren: A journey from inhibition to biosensing

Abstract

For the first time, a novel electrochemical biosensor was fabricated based on modification of a rotating glassy carbon electrode with multi-walled carbon nanotubes-ionic liquid, and molecularly imprinted polymers (MIPs) in which renin (Rn), and aliskiren (AK) were used as templates. By immersion the biosensor in Rn, AK, and their binary system (AK-Rn) solutions, the species (Rn, AK, and AK-Rn) were entrapped within the pathways of the MIPs. These processes and investigation of the inhibition of the Rn by AK helped us to obtain higher electrochemical signals for a good monitorization of the system. The effects of experimental parameters on response of the biosensor to AK were optimized by a small central composite design to obtain the highest response. Hydrodynamic cyclic voltametric (HCV), hydrodynamic differential pulse voltammetric (HDPV), and hydrodynamic linear sweep voltammetric (HLSV) data obtained and recorded in order to be analyzed by classical methods and multivariate curve resolution-alternating least squares (MCR-ALS) as an advanced chemometric method. The results of molecular dockings, classical and chemometric analyses confirmed that the Rn was strongly inhibited by the AK which was good evidence to develop a novel biosensing system for determination of Rn. A novel biosensor was developed for determination of the Rn which had an acceptable performance in determination of Rn in the range of 0–9 fM. This approach opened a new way for investigation of enzymes' inhibition, and developing a new generation of electrochemical biosensors for medical and biomedical applications.