Researchers develop a fast and efficient way to build amino acid chains

Scientists often build new protein molecules by chaining groups of amino acids. These amino acid chains, called polypeptides, are the building blocks for drug development and the creation of new biomaterials.

The process of constructing polypeptides is, however, difficult. Researchers say they have developed a new method for making new polypeptides that is faster, simpler and less expensive than previously available. The new approach uses a streamlined process that purifies amino acid precursors and constructs polypeptides at the same time, unlike previous methods in which processes were separate, laborious, and time consuming.

The manufacture of polypeptide chains has always been a very complicated process, said Jianjun Cheng, professor of materials science and engineering at the University of Illinois, who led the new research. The synthesis and purification of amino acid precursors, namely N-carboxyanhydride, or NCA, requires tedious efforts, and the construction of polypeptide chains takes hours to days, he said.

"The field has never grown, in part because the synthesis of polypeptides is so complicated," Cheng said. "The NCA contains a lot of impurities that are difficult to remove, and up to now, the synthesis of high quality polypeptides required an ultrapure NCA."

In biological cells, enzymes called ribozymes link amino acids to form proteins, Cheng said. This process takes place in the presence of water, salt and many other molecules. However, it is very difficult to replicate this process in the laboratory. Current methods require researchers to use purified NCA molecules and construct chains in a waterless environment.

Cheng and his colleagues have drawn their inspiration from ribozymes, which excel in rapidly producing amino acid chains while isolating them from the cell environment. The team has developed a system that mimics the function of ribozymes, rapidly building amino acid chains while eliminating molecules that can contaminate the system. This allows researchers to build the desired strings with non-pure NCAs.

"It's the first time since the discovery of the NCA molecule in 1906 that we are able to build long chains with the aid of unpurified NCA," Cheng said.

"I worked on the purification of NCA for several years and found it very painful because the process required waterless conditions and was a technical challenge," said postdoctoral researcher Ziyuan Song, Cheng's laboratory member. "That's why there are not a lot of research groups working in this area, because with this method we can attract more people and find more applications."

The method can be used in the fields of chemistry, biology and industry, where protein chains are commonly used as building blocks for assembling useful molecules, said the researcher.

"Previously, the industry needed specialized chemists like us to make these building blocks," Cheng said. "Our new protocol allows anyone with basic chemistry skills to create the desired polypeptides in a matter of hours."

Researchers are exploring ways to intensify the process and explore all the chemical and biological applications allowed by the new approach.

The researchers report their findings in the Proceedings of the National Academy of Sciences.