Peptide ligation

Protein-peptide ligation by amide bond formation... 

Shogren-Knaak, M.A., Fry, C.J. and Peterson, C.L. (2003) A native peptide ligation strategy for deciphering nudeosomal histone modifications. The Journal of Biological Chemistry, 278, 15744-15748. 

Peptide ligation strategies used so far have mainly been used for protein total synthesis and protein engineering purposes. The ability to prepare perfectly mono-disperse and relatively high molar mass peptides with precise control over the a-amino acid sequence could also afford unprecedented opportunities for the development of novel biologically-inspired supramolecular architectures and materials. As a final, recent, example, the preparation of a protein[2]catenane using NCL is shown in Figure 6.6.5 [34]. 

Amino acid derivatives for peptide ligation site HS. HS. /... 

Scheme 5. Schematic representation of the minimal au-tocatalytic reaction cycle of a self-replication a-helical peptide. The peptide fragments E and N are preorientated at the template through hydrophobic, interhelical interactions. The amide bond formation leads to an identical copy of the template, which further accelerates the peptide ligation in the autocatalytic cycle.

To better simulate the behavior of Fe-S clusters in the protein environment, a logical step is to ligate the clusters to actual cysteinyl peptides. Peptide-ligated clusters can be prepared via ligand exchange reaction (17) or cluster reconstitution using FeCb, Na2S, a reductant, and the peptide in aqueous buffer. 

Wallace CJ. Peptide ligation and semisynthesis. Curr. Opin. Biotechnol. 1995 6 403-410. 

The step from posttranslationally modified synthetic peptides to proteins, required for studying their central role in trafficking pathways and signaling networks, represents a challenge to future chemists. Only the newly developed peptide ligation procedures could possibly have a major impact. 

Synthetic peptides may be linked to create even longer molecules. Using specially developed peptide ligation methods, proteins of 100 amino acids or more can by synthesized in very pure form. These methods enable the construction of even sharper tools for examining protein structure and function. 

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