Insertion of amino acids can increase the activity of biological peptides by 40 times

Scientists at the Federal Institute of technology in Lausanne, Switzerland, have recently synthesized an amino acid that can shape the structure of active peptides and enhance their efficacy Experiments show that the activity of the amino acid can be increased by more than 40 times when it is inserted into the polypeptide with biological activity With this achievement, a series of new drugs are expected to be developed Relevant papers were published in the journal Nature chemistry At present, our commonly used drugs are mainly made of two kinds of substances, one is natural polypeptide substance, the other is protein, both of which are composed of natural amino acids Although there are many kinds of polypeptides and proteins, only 20 kinds of natural amino acids can be synthesized Each amino acid has different structure and chemical properties Different combinations of amino acids produce different peptides and proteins with different characteristics and functions Until recently, the vast majority of amino acid based drugs were made of amino acids that existed in nature, such as hormones, insulin, antibiotics, cyclosporine, etc But the emergence of a variety of new diseases and the evolution of original bacteria and viruses require scientists to develop new and more effective drugs One way to meet this demand is directed evolution, that is, to simulate the development of nature in the laboratory and develop new peptides and proteins A team led by Christian Hines of the Federal Institute of technology in Lausanne has developed a synthetic amino acid with a unique structure that can significantly improve the efficacy of therapeutic peptides and proteins, according to the physicist organization network on September 1 (Beijing time) This synthetic amino acid has a very similar structure to a natural amino acid called cysteine Cysteine contains sulfur groups that are not found in other natural amino acids, which enables it to combine with another cysteine to form a new structure, thus affecting the function of peptides and proteins The researchers first designed five cysteine like amino acids and integrated them into the structure of two bioactive peptides, one can inhibit cancer-related enzymes, the other can block the receptors found in neurons Tests show that the activity of new drugs is nearly 40 times higher than that of traditional drugs "It's very surprising," Heins said Generally, if you mess with natural molecules, you can only make things worse In this case, we find that on the contrary, we get the desired result In the study, we learned that the structure of diversity in peptide library is the key to achieve good combination and better efficacy With this new amino acid, a highly diverse peptide structure can be produced " Dicyclic peptides have been considered to be able to replace the small molecules or large antibodies used in common drugs to treat diseases This new therapeutic peptide will play an important role in drug design in the future Heins said that they have made plans to use bicyclic peptides to develop drugs for various diseases, and the next step is to use the new amino acid for directed evolution experiments Editor in chief circle The natural structure derived from genetic evolution has a conservative presupposition, and has been verified for a long time From time to time, scientists use bold creativity to divide and combine it again, and try to create a more optimized structure with the original structure as the guide This time, Swiss scientists have applied such imagination to the basic unit of protein, the material basis of life The newly synthesized amino acids can increase the activity intensity, improve the physical and chemical properties and promote the efficacy of drugs It remains to be seen whether the natural molecules that have been "stirred" can play an important role in drug design in the future (editor in charge: Li Hao)