Degussa Aktiengesellschaft

Hoechst Aktiengesellschaft

Hans-Dieter Jakubke

Karlheinz Drauz

Andreas Bommarius

Uwe Eichhorn

Matthias Kottenhahn

Matthias Schuster

Peter Kuhl

Dirk Ullmann

Aavo Aaviksaar

The invention concerns a process for the enzymatic preparation of protected di- and oligopeptides and the separation of the protective groups used. The process according to the invention enables peptides to be synthesized simply and economically and the protective group to be separated carefully. The process comprises three reaction steps: 1. Preparation of N-carbamoyl amino acid or N-carbamoyl amino acid derivatives; 2. Formation of the peptide bond between the carbamoyl-protected electrophile and nucelophile; and 3. Separation of the carbamoyl-protective group.

Process for preparing peptides and N-carbamoyl-protected peptides

A water-supported enzymatic reaction is carried out with the substrate and the enzyme present in the solid phase. Either the water does not form a liquid continuum around substrate and enzyme, or the water acts at least partially out of the gas phase, or the water required for the reaction is added via a solid, or at least a part of the water required for the reaction is transferred by means of solid body contacts or by a combination of these means. The reaction mixture can be mixed by ultrasound or turbulence, e.g. in a fluidized bed, or both.

Enzymatic reactions and apparatus for carrying them out

The biocatalytic production of a peptide is carried out with a zymogen instead of the customarily used protease. Since zymogens are proteolytically inactive precursors of proteases, proteolytic side reactions are largely suppressed. Preferably, amino acid esters or peptide esters and C-terminally derivatized amino acids or peptide fragments are coupled to each other. The reaction can also take place in a frozen, aqueous medium. In particular, chymotrypsinogen, trypsinogen, pepsinogen, prorennin or procarboxypeptidase are suitable as zymogens.

Method of producing peptides

Process for preparing peptides

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Leipzig, Germany

Hans-Dieter Jakubke