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The evolution of chemical ligation technology: how a new era of protein synthesis was ushered in in 1994?
With the advancement of science and technology, the application of chemical ligation technology in protein synthesis has received increasing attention. Especially in 1994, the emergence of Native Chemical Ligation (NCL) provided a new method for the synthesis of larger and more complex protein chains. This technology not only significantly improved the efficiency of protein synthesis, but also expanded scientists' capabilities in this field. research possibilities.
Basic principles of Native Chemical Ligation
Native Chemical Ligation is a technology that covalently combines two unprotected peptide segments to synthesize a larger peptide chain, mainly relying on the reaction of the thiol group of the cysteine residue located at the N-terminus. This reaction is usually performed in a neutral pH aqueous buffer, such as a solution of the amino acid in 6 M hydrochloric acid.
In Native Chemical Ligation, the ionized thiol group of the N-terminal cysteine attacks the C-terminal thioester of another unprotected peptide, forming a thioester intermediate that is quickly passed through Intramolecular S,N-acyl transfer recombines into native amide (peptide bond).
Historical background of technology
Native Chemical Ligation is not an overnight technology. Its birth can be traced back to 1992, when Stephen Kent and Martina Schnölzer of the Scripps Research Institute first proposed the concept of "chemical ligation", which is a chemical way to combine A method of covalently condensing unprotected peptides together.
In 1994, Philip Dawson, Tom Muir, and Stephen Kent reported Native Chemical Ligation. This technology not only helped to form native peptide bonds, but also effectively overcome many limitations of traditional synthesis techniques.
The core feature of Native Chemical Ligation is its strong chemical selectivity and regioselectivity, which are crucial for most protein synthesis.
Current applications and challenges
With the widespread application of Native Chemical Ligation in modern chemical protein synthesis, many innovative synthesis strategies have emerged. Using this technology, scientists can synthesize large proteins that would otherwise be impossible to make, which has a positive impact on biomedical research, vaccine development and protein engineering.
With Native Chemical Ligation, both post-translationally modified proteins and complex proteins containing non-coding amino acids can be synthesized with near-quantitative efficiency. This is particularly important for specific applications, particularly in the areas of new drug development and gene therapy.
The "green" characteristics of Native Chemical Ligation are reflected in its excellent atom economy and the ability to use harmless solvents, making it occupy a place in the field of environmentally friendly chemical synthesis.
Future direction
With the deepening of research, the potential of Native Chemical Ligation has still not been fully exploited. Not only in the development of new chemical reactions, but also other types of protein synthesis technologies, such as Expressed Protein Ligation and the use of other types of peptide ligations. In this context, continuing to explore other available connection strategies is also one of the important directions for future research.
In this era of rapid technological change, how will the development of Native Chemical Ligation technology affect our understanding and application of biomolecule synthesis?
