A team of researchers has developed a faster and easier way to create unnatural amino acids and assemble them into peptides. This is a breakthrough method that has the potential to accelerate peptide research and provide new tools for designing drugs.
team of University of CaliforniaThe University of Santa Barbara has developed a new method to synthesize and assemble unnatural amino acids into peptides. This could improve peptide research and inform future preclinical drug research.
technique This allows scientists to access the more than 22 amino acids found in nature with much higher efficiency. This method eliminates several difficult steps required by traditional approaches by producing amino acids in a form ready for peptide synthesis.
“The key advantage is that these amino acids are already obtained from the process in a form that can be used directly for peptide production without the need for additional modification steps,” said first author Phil Kohnke, a doctoral student in the lab of senior author Limin Zhang in the Department of Chemistry and Biochemistry. “Compared to existing approaches, this is one of the simplest and most widely useful methods reported to date.”
components of life
Peptides are short chains of amino acids that make up proteins. Although proteins are larger, more complex, and made up of multiple peptides, the order of the amino acids in both peptides and proteins defines their structure and function. Nature typically relies on 22 amino acids to build proteins, including the 20 standard amino acids encoded by DNA and two produced by other mechanisms.
Peptides are short chains of amino acids that make up proteins.
While natural amino acids are cheap and readily available, unnatural amino acids are much more difficult to produce and incorporate. Zhang’s team has created a process that overcomes these challenges with a direct chemical route that can produce amino acids that can be readily used for peptide synthesis.
Two-step synthesis approach
This method utilizes gold catalysts to convert inexpensive chemical components into amino acids with precise handedness, a property important for biological activity. Amino acids are then attached to the peptide using a resin scaffold, allowing the chain to grow in a controlled order.
Traditional peptide synthesis methods require both the removal of the amino-terminal protecting group and the activation of the acid terminus of each amino acid. In contrast, this new approach produces amino acids with acid groups already ready for reaction, so only the amino groups need to be unmasked. The use of resin scaffolds also simplifies purification. Once the peptide is complete, it can be removed from the scaffold and cleaned, eliminating the need for tedious extraction from solution.
Expanding the possibilities of research and medical care
“Many existing methods either require many time-consuming steps, work only on a limited set of molecules, or require further manipulation before the peptide is ready for synthesis,” Kohnke said. “The new technology largely solves these problems and easily and cheaply produces amino acids that are immediately useful for peptide synthesis.”
For biochemists, materials scientists, and medical researchers, having access to a greater variety of amino acids is critical.
Zhang highlighted the potential for peptide therapeutic applications, noting that since insulin was first synthesized, more than 80 peptide-based drugs have been approved around the world. Peptides containing unnatural amino acids can be made more resistant to enzymes or shaped to fit more effectively into target receptors.
Although the current study is primarily a breakthrough in chemistry, it has the potential to inform future preclinical drug research by providing medicinal chemists with a richer toolkit for designing and testing peptide therapeutics.
The team is now seeking help to make the methodology available to researchers working in drug development and materials science.