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Bacterial Detection & Identification Using Electrochemical Sensors

Bacterial Detection & Identification Using Electrochemical Sensors

Published on: April 23, 2013

A novel cell-based sensor detecting the activity of individual basic proprotein convertases.

Karin Löw^1,2, Kornelia Hardes³, Chiara Fedeli¹

¹Institute of Microbiology, University Hospital Center, University of Lausanne, Switzerland.

The FEBS Journal

|July 6, 2019

Summary

A new cell-based sensor, basic PC sensor (BPCS), enables rapid screening of drug candidates targeting proprotein convertases (PCs) and their selectivity. This tool aids in developing novel therapeutics for various human diseases.

Keywords:

furin high-throughput screening inhibitor proprotein convertase sensor

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An Aptamer-based Sensor for Unchelated GadoliniumIII

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Area of Science:

Biochemistry
Molecular Biology
Drug Discovery

Background:

Basic proprotein convertases (PCs) are crucial drug targets for human diseases.
Developing selective PC inhibitors is difficult due to substrate similarities and lack of structural data.
Current screening methods using soluble enzymes may not reflect cellular conditions.

Purpose of the Study:

To develop a novel cell-based molecular sensor for screening basic PC inhibitors.
To enable rapid assessment of inhibitor selectivity against individual basic PCs within cells.
To facilitate the discovery of specific small-molecule inhibitors for therapeutic applications.

Main Methods:

Development of the basic PC sensor (BPCS) using Gaussia luciferase and a sortilin-1 membrane anchor.
BPCS relies on PC-mediated cleavage of a linker to release luciferase.
High-throughput screening of candidate peptidomimetic inhibitors using the BPCS assay.

Main Results:

BPCS successfully distinguished between general and selective PC inhibitors in a high-throughput format.
The cell-based sensor accurately assesses inhibitor activity within the cellular context.
Demonstrated the utility of BPCS for identifying specific small-molecule inhibitors.

Conclusions:

BPCS is a robust, cost-effective tool for identifying selective basic PC inhibitors.
The cell-based approach allows targeting not only the enzyme but also related cellular factors.
BPCS offers a significant advantage for discovering novel direct or indirect PC inhibitors for therapeutic use.