Process for producing pentapeptides and intermediates for use in the synthesis

US5252464A · kind A · utility

Assignee

• Carlsberg Biotechnology Ltd. A/S · DK

Inventor

• Anders Jorgen Andersen · Kokkedal, DK

Key dates

• Filing date: Sep 4, 1992
• Grant date: Oct 12, 1993
• Expiry date: Sep 4, 2012

Classification

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

Abstract

Pentapeptides having the formula H-Asp-Ser-C-Pro-Arg-OH, where Asp, Ser, Pro and Arg may have L- or D-configuration, and C denotes Asp or Asn in L or D configuration, are synthesized by reacting in an aqueous medium Y.sub.2 -Pro-OH, wherein Y.sub.2 is a protective group, with Arg-Ro, wherein Ro is OH or is as defined below for R.sub.1 below, to form Y.sub.2 -Pro-Arg-Ro, which is deprotected, if necessary under conversion to Pro-Arg-R.sub.1, wherein R.sub.1 is an enzymatically cleavable .alpha.- carboxy substituting group selected form esters, amides, anilides, hydrazides or L-amino acid esters, and thereafter reacting Y.sub.3 -C(Z.sub.3)-OH with Pro-Arg-R.sub.1 to form Y.sub.3 -C(Z.sub.3)-Pro-Arg-R.sub.1 which is deprotected to C-Pro-Arg-R.sub.1, and then reacting Y.sub.4 -Ser-OH with C-Pro-Arg-R.sub.1 to form Y.sub.4 -Ser-C-Pro-Arg-R.sub.1, which is deprotected to Ser-C-Pro-Arg-R.sub.1, and reacting Y.sub.5 -Asp(Z.sub.5)-OH with Ser-C-Pro-Arg-R.sub.1 to form Y.sub.5 -Asp(Z.sub.5)-Ser-C-Pro-Arg-R.sub.1, which is deprotected to the intermediate Asp-Ser-C-Pro-Arg-R.sub.1, and finally removing the group R.sub.1 with an enzyme, preferably trypsin to form Asp-Ser-C-Pro-Arg, or removing …