Scientists at the Federal University of Technology in Lausanne, Switzerland, have previously synthesized an amino acid that creates the structure of an active peptide and improves its efficacy. Experiments have shown that insertion of such amino acids into biologically active peptides can increase their activity by more than 40-fold. The results hold promise for the development of a whole new and improved range of drugs. The paper is in the journal Nature Chemistry.
At present, the common drug key is made of two types of chemicals, one is a naturally occurring peptide chemical, the other is a protein, both of which are made up of natural amino acids. Although there are many kinds of peptides and proteins, there are only 20 kinds of natural amino acids that produce them. Each amino acid has a different structure and physical properties, and the different composition of amino acids gives rise to peptides and proteins with different characteristics and functions.
Until recently, most amino acid-based medicines, such as hormones, insulin, antibiotics, and cyclosporine, were made from amino acids that are naturally present in nature. However, with the emergence of a variety of new diseases and the evolution of the original pathogen and virus infection, it is necessary for experts to develop newer and more reasonable drugs. One way to consider this requirement is directed evolution, in which newer peptides and proteins are developed in the laboratory to mimic the trends of nature.
An elite team of researchers led by Brad Heins of the Ecole Polytechnique Federal-Lausanne (EP-Lausanne) has developed an amino acid with a distinctive structure that significantly enhances the effects of therapeutic peptides and proteins. “These generated amino acids have a very similar structure to a natural amino acid called cysteine.” Cysteine has a sulfur group that is not found in other natural amino acids, which enables it to bind closely to another cysteine, producing a new structure that can impair the action of peptides and proteins.
The RESEARCHERS FIRST DESIGNED FIVE AMINO ACIDS similar TO CYSTEINE AND FUSED THEM INTO A CONSTRUCT OF TWO BIOACTIVE PEPTIDES, ONE THAT BLOCKS ENZYMES involved IN CANCER AND ONE THAT BLOCKS RECEPTORS FOUND IN NERVE CELLS. The test showed that the drug activity was nearly 40 times higher than that of traditional drugs.
“It was very surprising,” Hynes said. In general, if you mess with natural molecules, you just make things worse. And in such cases, you find that the opposite is true, and you get the desired result. In the study, it was learned that the diverse structure of the peptide library was fundamental to achieving good fusion and greater efficacy. “With this new class of amino acids, we can produce peptide constructs with diverse aspect ratios.”
Bicycling peptides have been proposed to replace the small molecules of water or large antigens used in general pharmaceuticals in the treatment of diseases. This new class of therapeutic peptides will play an important role in future drug design. Hynes said they have already developed a plan to use dicyclopeptides to develop drugs for a variety of diseases, and the next step is to test directed evolution with this new class of amino acids.
Post time: Nov-29-2024