Medicine is evolving at a really rapid pace, and now we have a new era in drug development. Check out the latest reports involving peptides below.
New era for drug development
Scientists have been struggling for decades to develop oral drug therapy for many proteins that are essential for treating various diseases.
Traditional small molecules fail to bind to proteins with flat surfaces or require specificity for particular protein homologs.
Larger biologics that can target such proteins require injection, which limits patient convenience and accessibility.
However, in a new study published in Nature Chemical Biology, scientists from the laboratory of Professor Christian Heinis at EPFL have achieved a significant milestone by developing a new class of orally available drugs. This breakthrough has addressed a long-standing challenge in the pharmaceutical industry.
“There are many diseases for which the targets were identified but drugs binding and reaching them could not be developed,” says Heinis.
“Most of them are types of cancer, and many targets in these cancers are protein-protein interactions that are important for the tumor growth but cannot be inhibited.”
The study concentrated on cyclic peptides, which are flexible molecules recognized for their exceptional affinity and specificity in binding complex disease targets.
However, creating cyclic peptides as oral medications has been problematic since they are quickly digested or poorly absorbed by the gastrointestinal tract.
“Cyclic peptides are of great interest for drug development as these molecules can bind to difficult targets for which it has been challenging to generate drugs using established methods,” says Heinis.
“But the cyclic peptides cannot usually be administered orally—as a pill—which limits their application enormously.”
The research team focused on the enzyme thrombin, which plays a crucial role in blood coagulation and is a key target for preventing and treating thrombotic disorders such as strokes and heart attacks.
In order to develop cyclic peptides that can effectively target thrombin and remain stable, the scientists utilized a two-step combinatorial synthesis strategy to synthesize a large library of cyclic peptides with thioether bonds.
These bonds enhance the metabolic stability of the peptides and make them suitable for oral consumption.
“We have now succeeded in generating cyclic peptides that bind to a disease target of our choice and can also be administered orally,” says Heinis.
“To this end, we have developed a new method in which thousands of small cyclic peptides with random sequences are chemically synthesized on a nanoscale and examined in a high-throughput process.”
