CONTINUOUS ENZYMATIC PROCESS FOR PREPARING PEPTIDES

摘要

Peptide preparation is carried out by a continuous process by supplying a serine protease or peptidase enzyme retained in a reaction vessel with an alkyl ester of an N-protected amino acid or oligopeptide and a recycle stream containing an amino acid or oligopeptide to form an N-protected chain extended peptide, separating the N-protected chain extended peptide by adsorption on a hydrophobic absorbent, and eluting and recovering the adsorbed N-protected chain extended peptide. Adsorption is carried out without adjusting the pH from that in the reaction vessel, and adsorber effluent is recycled to the recycle stream. The protease or peptidase enzyme may be immobilized, and there is substantial exclusion of organic solubilizers in the reaction vessel. A preferred N-protecting group is an N-phenacyl group. The N-protecting group can be separated from the N-protected chain extended peptide with a deprotecting enzyme to recover the chain extended peptide. Apparatus is used that provides for continuous operation of the process.