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Native Chemical Ligation of Peptides and Proteins.
Current Protocols in Chemical Biology 2019 January 16
For over 20 years, native chemical ligation (NCL) has played a pivotal role in enabling total synthesis and semisynthesis of increasingly complex peptide and protein targets. Classical NCL proceeds by chemoselective reaction of two unprotected polypeptide chains in near-neutral-pH, aqueous solution and is made possible by the presence of a thioester moiety on the C-terminus of the N-terminal peptide fragment and a natural cysteine residue on the N-terminus of the C-terminal peptide fragment. The reaction yields an amide bond adjacent to cysteine at the ligation site, furnishing a native protein backbone in a traceless manner. This unit highlights a number of recent and powerful advances in the methodology and outlines their particular uses, facilitating application in the synthesis of challenging protein targets. © 2019 by John Wiley & Sons, Inc.
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