Fragment condensation, solid-phase protein synthesis

The most successful method of fragment condensation for the synthesis of polypeptides and proteins in solution phase is NCL, reported by Dawson for the first time in 1994 [7]. This was a significant contribution because NCL overcomes one of the main limitations of solid phase peptide synthesis (SPPS), namely the production of long peptide sequences (>50 amino acid residues) [1, 3, 29]. NCL may be used in both solution and solid phases solution phase NCL has been used for the synthesis of small peptides and cyclic peptides [30-32] whereas SPPS is more widely applied in polypeptide and protein synthesis. 

An alternative to the synthesis of proteins by classical fragment synthesis in solution or by solid-phase synthesis on a support is the use of enzyme-catalyzed condensation of amino acids or peptides. This possibility was first demonstrated in 1938 91 with the synthesis of poorly soluble benzoyl-leucyl-leucine anilide by papain catalysis. After many years, this approach was extended to the preparation of peptide hormones such as Leu-enkephalin 92 and dynorphin(l -8).[93 This was made possible by the use of highly purified enzymes and by careful control of reaction conditions. The basic principles of protease-catalyzed peptide bond formation have been discussed.194 ... 

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