Process Considerations for the Synthesis of Peptides

Production of peptides on a productive scale represents the ultimate goal of technological development and presents several challenges that have to be addressed. 

More than 40 therapeutic peptides are now in the market, which represents a considerable increase, since less than 10 were in the market by 1990. A much higher number of therapeutic peptides are in the different phases of approval. The therapeutic application of peptides has an enormous potential, which has been enhanced by the advances in the fields of formulation and administration of pharmaceuticals. Several of those peptides are now being produced at large scale (Guzman et al. 2007). 

The large number of critical variables in an enzymatic process makes its optimization cumbersome. However, many of the limitations of chemical synthesis can be overcome by protease synthesis. The high specificity and high reactivity under mild operation conditions, which is characteristic of enzymatic processes, can have a 

The preparative synthesis took place in stirred batch reactors of 200-500 mL volume, with a sintered plate at the bottom, allowing the retention of the immobilized enzyme after discharge of the reacted medium. The reactions were performed in organic solvent (ethyl acetate or acetonitrile) at controlled initial water activity (a = 0.1). For KCS reactions, only a very small amount of water is produced so that its concentration can be considered constant during the reaction. After addition of the biocatalyst (previously equilibrated) and substrates, the water content was 

---