Solid-phase methods are now the principal method for chemical peptide synthesis. However current solid-phase procedures generally require a large volume of organic solvents, the safe disposal of which is an important environmental issue. The development of synthesis methods that do not use organic solvents would be desirable. In recent years, we have been driven to focus on the development of a method for peptide synthesis in water, which is an environmentally friendly solvent. SPPS is commonlyperformed via a base-labile Fmoc strategy. However, Fmoc-amino acids are sparingly soluble in water and have been considered inappropriate for in-water peptide synthesis. With the aim of achieving aqueous SPPS, we developed in-water synthesis protocols using water-dispersible nanoparticulate Fmoc-amino acids. This technology uses suspended nanoparticle reactants for the coupling reaction to overcome the solubility problem. However, there are two main problems with this nanoparticle approach; (i) slow reaction rates compared to general peptide synthesis in ordinary organic solvents (ii) poor yields for the synthesis of long peptides
MW-assisted SPPS is already a conventional technology and automated peptide synthesizers equipped with MW capability are commercially available. The main advantages of MW assisted chemistry are shorter reaction times and higher yields. A trial of MW assisted in-water solid-phase synthesis of Leu-enkephalin using Boc-amino acids has been reported by Albericio previously. Currently, Fmoc-amino acids are routinely used as building blocks for SPPS. With this in mind, we have been engaged in water-based MW-assisted SPPS using Fmoc amino acid nanoparticles and have established an efficient aqueous-based synthesis of the acyl carrier protein (65-74) peptide [1]. And We also developed an efficient protocol for negligible Cys and His racemizaiton as demonstrated by the successful synthesis of oligopeptides by our aqueous-based MW-assisted method using Fmoc strategy [2,3].