Synthesis of Large Peptides in Solution

T Kimura, M Takai, Y Masui, T Morika, S Sakakibara. Strategy for the synthesis of large peptides an application to the total synthesis of human parathyroid hormone [hPTH (1-84)]. Biopolymers 20, 1823, 1981. 

S Sakakibara. Synthesis of large peptides in solution. Biopolymers (Pept Sci) 37, 17, 1995. 

Y Nishiuchi, H Nishio, T Inui, J B6di, F Tsuji, T Kimura, S Sakakibara. Total synthesis of green fluorescent protein (GFP), a 238 residue protein from jellyfish Aequorea victoria, in S Bajusz, F Hudecz, eds. Peptides 1998. Proceedings of the 25th European Peptide Symposium. Akademiai Kiado, Budapest, 1999, pp 36-37. 

Y Nishiuchi, H Nishio, J Bodi, T Kimura. Combined solid-phase and solution approach for the synthesis of peptides and proteins. J Pept Sci 6, 84, 2000. 

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Despite the breakthrough associated with Merrifield s approach, there are several limitations such as the discontinuous nature of the reaction, the need for large excesses of reagent and the mechanical instability of the polymer matrix. An early solution to the restrictions imposed by Merrifield s polystyrene supported batch process was the use of commercially available benzyl alcohol-functionalized silica (used for H PLC columns). This was initially derivatized with the first member of the peptide chain to be propagated. The synthesis of a tetrapeptide in flow was completed in half the time required for the equivalent batch mode assembly and required significantly smaller excesses of the solution-phase reagent [92],... 

Synthesis of peptides in solution is currently practiced in very few laboratories, or is applied in the case of large-scale peptide synthesis. Multiple solution... 

SAPPHO is a powerful new innovative technology for the automated large scale synthesis of peptides in solution phase, which can lead to significant cost saving of up to 50 % compared to the traditional technologies (in homogeneous phase or Merrifield phase). 

Although chemical synthesis of peptides and proteins has developed substantially in recent decades, it does require use of toxic reagents, large amounts of expensive reagents, and often suffers from incomplete reactions that significantly reduce final product purity. Chemical synthesis can be performed in solution, on a solid phase, or by a combination of both. Solution-phase synthesis has been the method of choice for large-scale preparation, but developments in solid phase tools have enabled its use also. 

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