NCL, Native chemical ligation

CHO Chinese hamster ovary NCL native chemical ligation SPPS solid-phase peptide synthesis... 

EPL Expressed protein ligation NCL Native chemical ligation PrP Prion protein... 

Scheme 34 Overview of native chemical ligation (NCL). Two unprotected segments react in a reversible thiol/thioester reaction only the thioester product between the C-terminal thioester and the N-terminal cysteine can react further to form the desired amide bond via nucleophilic attack of the cysteine amine group.

At present, it appears that the most powerful method for the coupling of two unprotected peptide segments is the Native Chemical Ligation (NCL) developed by Dawson and Kent [21], As indicated by its name, NCL gives rise to the formation of a natural peptide bond. This reaction was described in principle as early as 1953, by Wieland, who reported that the reaction between the (S)-valine thiophenyl ester 22 and cysteine 23 proceeded by transfer of... 

The technique of native chemical ligation (NCL) or expressed protein ligation (EPL) (42) tremendously expanded the scope of peptide/protein synthesis. This approach also has been adopted for the construction of neoglycoproteins. For complete synthetic... 

The native chemical ligation (NCL) has enjoyed tremendous success as one of the few methods for C-terminal protein modification. In its most general form, this approach is a ligation between a peptide that contains a C-terminal thioester and a... 

Figure 9 Modification of the C-terminus through native chemical ligation (NCL).

Figure 1 Native chemical ligation (NCL) between two unprotected peptide segments. The initial transthioesterification reaction leads to an intermediate that undergoes an S to N-acyl shift via a five-membered cyclic transition state and generates a native amide bond at the ligation site.

Figure 13 Semisynthesis of homogeneous glycosylated GlyCAM-1 by expression protein ligation (EPL) combined with native chemical ligation (NCL) of recombinant protein and synthetic glycopeptide fragments.

---