Native chemical ligation mechanism

Jung JP, Jones JL, Cronier SA et al (2008) Modulating the mechanical properties of self-assembled peptide hydrogels via native chemical ligation. Biomaterials 29 2143-2151... 

In order to perform a native chemical ligation, two prerequisites have to be fulfilled. First, the C-terminal fragment (2) has to contain a Cys residue (which in principle could also be Ser, although it is less reactive) at the N-terminus. The N-terminal fragment (1) possesses a C-terminal thioester. The reactivity of this activated carboxyl group can be tuned by proper selection of the thiol substituent. For example, aromatic groups are more reactive than alkyl groups. The mechanism of peptide bond formation encompasses two steps. In a first reversible reaction the... 

Figure 8 Mechanism of amide bond formation in native chemical ligation.

Shortly after the initial discovery of native chemical ligation, a number of studies were subsequently conducted with the aim of establishing the scope of the ligation methodology and deciphering the subtleties of the reaction mechanism. In particular, the dependence of the rate of ligation oti the nature of the C-terminal peptide thioester moiety has been extensively studied. 

Johnson ECB, Kent SBH (2006) Insights into the mechanism and catalysis of the native chemical ligation reaction. J Am Chem Soc 128 6640-6646... 

Scheme 9 Mechanisms of (a) native chemical ligation and (b) expressed nx>tein ligation...

Wang C, Guo Q-X, Fu Y (2011) Theoretical analysis of the detailed mechanism of native chemical ligation reactions. Chem Asian J 6 1241-1251... 

Jung JP, et al. (2008) Modulating the Mechanical Properties of Self-Assembled Peptide Hydrogels via Native Chemical Ligation. Biomaterials. 29 p. 2143-51. 

---