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Revealing the miracle of protein synthesis: What is the secret of native chemical ligation?
With the rapid development of biotechnology, Native Chemical Ligation (NCL) has become an indispensable method in protein synthesis. Since it was proposed in 1994, this technology has attracted extensive research and application. The chemical reaction mechanism behind it and its application in synthesizing natural and modified proteins are amazing.
Reaction mechanism of native chemical ligation
In native chemical ligation, the anionic thiol group of the N-terminal cysteine attacks the C-terminal thioester of a second unprotected peptide chain, usually in an aqueous buffer at a pH of about 7. is being carried out. The reversibility and selectivity of this step make the reaction extremely specific and efficient in generating linked peptide chains.Historical BackgroundThe first step of the reaction, the exchange reaction of thiolate with thioester, is dependent on the addition of a thiol catalyst, which is also a key feature of the native chemical ligation method.
The history of native chemical ligation can be traced back to the concept of "chemical ligation" proposed by Stephen Kent and Martina Schnorzer in 1992. Two years later, Philip Dawson, Tom Mair and Stephen Kent extended this technology to native chemical ligation, creating a new method for efficient protein synthesis. This technology is not only novel, but also plays an important role in the synthesis of complex proteins.
Characteristics of native chemical ligation
The biggest advantage of this technology is that it can perform efficient peptide chain synthesis without releasing by-products. This has led to the widespread application of native chemical ligation in the synthesis of proteins and enzymes, and the ability to synthesize large molecular proteins with a scale of more than 300 amino acids.
Native chemical ligation is an important step towards sustainable chemistry due to its inherent "green" properties in terms of its atom economy and use of harmless solvents.
Application scenarios
The application range of native chemical ligation is quite wide. Recombinant DNA products obtained from genetic engineering can generate C-terminal thioesters, and these peptide chains can participate in native chemical ligation to generate large semi-synthetic proteins. In addition, synthetic peptides can be introduced into recombinant proteins, giving scientists more flexibility in editing the structure and function of proteins.
Technical Challenges and Future Directions
Although native chemical ligation has significant advantages in many aspects, it still faces some challenges in practical applications, such as the stability of the N-terminal cysteine and the selection of induced products. In addition, with the development of fine chemistry, researchers are trying to explore other biocompatible chemical reactions to further expand the potential of native chemical ligation.ConclusionThe native chemical connection method is undoubtedly a huge scientific breakthrough, but further research is needed in the future on how to enhance its stability and profitability.
The development of native chemical ligation in protein synthesis, from early concepts to today's mature technology, is a symbol of scientific progress. With in-depth research on this technology, more mysteries of chemical reactions may be uncovered in the future, and we may explore how to better use this technology to solve current challenges in the biomedical field. Behind all this, we can't help but wonder, how will future protein synthesis technology affect our lives and health?
