Amide Forming Chemical Ligation under Mild Reagent-Free Conditions

BACKGROUND: Despite the importance of amide (peptide) bonds, there are currently few methods for their preparation. The synthesis of amide bonds is generally limited to methods requiring the use of excess coupling reagents and side chain protected amino acid residues. These processes are inefficient and can prove difficult to use when joining large strands or fragments.

DESCRIPTION: Researchers at the University of California have developed a novel peptide ligation process to prepare native peptide bonds under mild, aqueous, reagent-free conditions, with water and carbon dioxide as the only by-products. The reaction involves direct coupling of alpha-keotacids and N-alkylhydroxylamines in a highly chemoselective amide bond formation process. Research has confirmed a high tolerance of this process to the presence of reactive functional groups including free amines, carboxylic acids, azides, and heterocycles, which demonstrates the potential of this reaction to serve as a peptide ligation process on both protected and unprotected substrates.

Experiments have demonstrated couplings that produced the desired amide in 50%-99% isolated yield without epimerization. The reactions are generally complete within 15 hours.

APPLICATIONS: Real-world applications of this technology include:

* the construction of complex organic molecules, including synthetic proteins;
* tandem ligation for complex biomolecule synthesis;
* the coupling of unprotected molecules; and * template-directed peptide synthesis.

REFERENCE: 2005-783

Type of Offer: Licensing



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