Researchers at Ben-Gurion University say they have identified certain proteins, families of proteins and protein interactions with one another, and pinpointed what drugs best interact with and inhibit them, using a combination of state-of-the-art chemical methods and next-generation sequencing analysis.
The new method could help create more drugs that are target-specific and inhibit the ability of proteins to develop into a range of diseases, including certain cancers. The discovery could lead to “groundbreaking” preventative and therapeutic treatment methods, the researchers said.
Current research on a wide variety of diseases, including some cancers, has revealed that certain proteins — large biomolecules that are located on cells — play a role in the development and progression of certain diseases, including cancer. Scientists now believe that observing the relevant interactions of these proteins could open the way to developing new drugs and ultimately to understanding some of the mechanisms responsible of the development of a whole range of diseases.
In a paper published in the October edition of Nature Communications, Dr. Niv Papo of Ben-Gurion University’s Department of Biotechnology Engineering and the National Institute of Biotechnology (NIBN) and his research team, including MSc student Si Naftaly and PhD student Itay Cohen, decided to map out all of these proteins and identify how they reacted with one another and how they reacted to specific drugs. They focused on neurodegenerative and bone diseases.
“Some protein families that sit on the surfaces of cells or that are secreted from cells all look alike, even if they have different functions,” Papo told The Times of Israel. “Some promote cancer, while others could suppress it. The latter may also be essential to normal physiology. We want to make sure drugs that are being developed target the bad proteins, and not the good ones. That is very difficult to do. It is difficult to make drugs differentiate between the different targets.”
Using a combination of chemical screening methods, based on specific recognition of various target proteins, and computational sequencing analysis, the researchers managed to label the various proteins and identify what drugs they interacted with, as well as what regions of the proteins best interacted with those drugs.
“The method allows you to identify hot spots and cold spots when developing new drugs to specific targets,” Papo said, “areas in the drug that are important for binding with the target and others that are not. Our research for the first time has been able to solve the challenge of knowing what drugs will target what specific targets, distinguishing between desired targets and off-targets.”
The research has provided an “unprecedentedly rich analysis of the binding specificity landscape of proteins in a rapid, cost-effective process,” he said.
This new approach will increase the understanding of the mechanisms and evolutionary origins of specific protein–protein interactions, he said, and help design specific drug inhibitors that can discriminate between structurally similar protein targets.
“The new approach thus offers great promise for designing target-specific therapeutics,” Papo said.