Process for the preparation of insulin derivatives, the B chain of which is lengthened c-terminally

US5015728A · kind A · utility

Assignee

• Hoechst GmbH · DE

Inventors

• Rainer Obermeier
• Rolf Geiger · Frankfurt am Main, DE
• Ulrich Grau · Emskirchen, DE

Key dates

• Filing date: Mar 23, 1988
• Grant date: May 14, 1991
• Expiry date: Mar 23, 2008

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y02P20/55
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The invention relates to a process for the preparation of an insulin derivative of the formula I ##STR1## in which R.sup.1 denotes H or H-Phe, R.sup.30 represents the radical of a naturally occurring L-aminoacid and R.sup.31 represents a physiologically acceptable organic group of neutral or basic character consisting of 1 to 3 .alpha.-aminoacids in which the terminal carboxyl function is present in the free form and which insulin derivative has an isoelectric point above 5.8, which comprises reacting an insulin of the formula I in which R.sup.30 denotes the radical of a genetically codable L-aminoacid and R.sup.31 represents OH or a protective group of the carboxyl function, with a peptide or aminoacid derivatives of the formula R-R.sup.30 -R.sup.31 consisting of 2 to 4 .alpha.-aminocacids, in which the terminal carboxyl function is in free form, in the presence of a trypsin-like endopeptidase at a pH value below the isoelectric point of the starting insulin.