Chemical ligation

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Chemical Ligation is a set of techniques used for creating long peptide or protein chains. It is the second step of a convergent approach. First smaller peptides containing 30-50 amino acids are prepared by conventional chemical peptide synthesis. They are then completely deprotected. Chemical ligation is the technique of selectively coupling these peptides in aqueous solution. With several coupling steps, proteins of up to 200-300 amino acids can be produced.

1 Methods of chemical ligation
2 Literature

[edit] Methods of chemical ligation

There are various techniques described in literature. All of them involve a first kinetically controlled coupling step. The intermediate rearranges to form the amid bond. Older techniques rely on the presence of cysteine. Methods using removable auxiliary groups overcome this limitation. The most important one is Staudinger ligation.

[edit] Prior Thiol Capture

Prior thiol capture was the first ligation process. It was developed in the 1980's. Through a disulfide bridge N-terminal cysteine is brought into proximity of the C-terminal amino acid of the other peptide.

[edit] Native Chemical Ligation

Developed in the 1990's native chemical ligation the method most commonly used. N-terminal cysteine reacts with a C-terminal thioester.

[edit] Expressed Protein Ligation

By exploiting natures inteins it is possible to prepare a recombinant C-terminal thioester. This removes the size restriction of the C-terminal thioester fragment. The recombinant thioester can be ligated to a synthetic peptide bearing an N-terminal cysteine. Native Chemical Ligations of this kind using recombinant C-terminal thioesters is known as Expressed Protein Ligation.

[edit] Acyl Initiated Capture

Acyl initiated capture is similar to Native Chemical Ligation only that peptide thioacid is brought into reaction with N-terminal bromo-alanine. The product is a peptide including cysteine.

[edit] Staudinger Ligation

With Staudinger Ligation, developed in 2000, peptide chains can be linked independently of the terminal amino acids. The method is based on the Staudinger reaction.