An approach towards efficient peptide synthesis in aqueous solution.

In all living organisms, all reactions involved in peptides and proteins synthesis proceeds exceedingly efficiently inside the cells in aqueous solution. An approach to efficient preparation of peptides in aqueous media is of great importance because the safe disposal of organic solvents is a vital environmental issue, and even more essential, the aqueous milieu is crucial to preserve the conformation of proteins, peptides, sugars and other potential drugs analogous to the native structure characteristic for physiological conditions. To perform successful peptide synthesis or modification of structures of proteins, the coupling reagent must be water-soluble and maintain its reactivity in water. This last term is crucial in the case of proteins because dominating concentration of water molecules promote substantial hydrolysis of any activated acyl derivatives, even considering relatively weak nucleophilicity of water. Unfortunately, there are only few reports presenting relatively resourceful results of peptide synthesis in aqueous solvents. Since 50ís, many research groups proposed several method for synthesis of peptide bond in water including mixed anhydrides (1), water-soluble carbodiimides (2), other water-compatible dehydrating agents (3), active esters (4) and water-soluble protecting group (5). In most cases , the scope of them is often limited to a mixture of solvents i.e., DMF/water and requires stepwise procedure. One of them, reported and considered as very promising for application in mixture of aqueous-organic media, involved application of