Artificial nanopore proteins that resemble natural ion channels have been developed by researchers in the US and Europe. These nanopores can be built into sensors to detect medically relevant substances.
Ion channels are essential for cells, allowing ions to pass through cell membranes. However, naturally occurring ion channels are difficult to work with due to their need to be solubilised in lipids. To overcome this challenge, a team led by David Baker and Anastassia Vorobieva designed pore-forming proteins from scratch using interconnected polypeptide chains called β-strands.
The researchers produced β-barrels with progressively larger pores and varied shapes. They then measured the electrical conductivity across phospholipid membranes incorporating these β-barrels. This allowed them to detect ions passing through the nanopores.
To create sensors for small molecules, the researchers designed “pseudocyclic” proteins that bind specific small molecule ligands. These pseudocyclic proteins were divided into fragments and attached to the nanopore proteins. In the presence of target molecules, the small molecule ligands bound to the fragments, temporarily blocking the ion channels.
The team demonstrated the ability to detect cholic acid, an indicator of liver disease, and methotrexate, an anticancer drug. They hope their method can be used for home testing of drugs and toxins that currently require routine clinical monitoring.
Source: https://www.chemistryworld.com/news/nanopore-proteins-designed-from-scratch-and-turned-into-biosensors/4019873.article