Carbodiimide-mediated peptide coupling remains to the most frequently used technique. As a major advantage, carbodiimides do not require prior activation of the carboxylic acid. Dicyclohexylcarbodiimide (DCC) has been predominantly used and is now well established. Since the generated urea derivatives as byproducts often have similar solubilities as the desired peptides, water-soluble carbodiimides have been developed whose corresponding ureas are readily separated by extraction with water. The most popular carbodiimide of this kind is EDC (N-(3- Dimethylaminopropyl)-N’-ethylcarbodiimide). Furthermore EDC or EDAC allow peptide coupling in alcohol or aqueous solutions involving proteins or peptide cyclizations.1
In solid-phase peptide synthesis, diisopropylcarbodiimide (DIC) is especially helpful due to the enhanced solubility of its urea derivatives.