Patent ID: 6323311
Filing Date: 2001-11-27
Classification: A61K,C07K,Y02P

Abstract:
A method for the synthesis of an insulin derivative having a hydrophilic compound coupled to the PheB1 amino group comprising:(a) coupling an acyl protective group to the GlyA1 and LysB29 amino groups of insulin comprising reacting insulin with a cyclic anhydride of a dicarboxylic acid in the presence of a tertiary amine thereby obtaining Gly-N.sup..alpha.A1, LysN.sup..epsilon.B29 -disubstituted insulin;(b) reacting the Gly-N.sup..alpha.A1, LysN.sup..epsilon.B29 -disubstituted insulin with an activated hydrophilic compound thereby covalently bonding the hydrophilic compound to the PheB1 amino group;(c) quantitatively hydrolyzing the acyl protective group from the GlyA1 and LysB29 residues, thereby obtaining the insulin derivative having the hydrophilic compound coupled to the PheB1 amino group.