Proteins : Researchers find potential new drug targets

"Many drugs bind to so-called GPCR proteins. But often the effect is quite unspecific. A Marburg research team may have found a way to change that.

With the help of computers, researchers at the University of Marburg have discovered previously unknown binding sites in an important protein family that could serve as targets for drugs. The scientists led by Peter Kolb and Moritz Bünemann, together with colleagues from Canada, examined so-called G protein-coupled receptors (GPCR). 

They transmit signals from the outside of a cell to its interior and play a role in inflammation and the transmission of sensory stimuli, for example.

 Almost a third of all prescription drugs attack GPCR proteins. "However, the coupling points used to date are often very similar," says Kolb; "That's why drugs are often not selective enough." For example, beta-blockers, which inhibit a GPCR in the heart, can trigger asthma attacks in the lung tissue.

Kolb and Bünemann's team used an algorithm to search for new binding sites in the structures of 113 different GPCR proteins. They found several "pockets" that have not previously been used as drug targets.

By changing two of the docking sites through mutations, the scientists were able to show that these structures are crucial for the function of the GPCR. The receptors could therefore be switched off by active substances that bind there."