Process for obtaining proinsulin possessing correctly linked cystine bridges

A process for obtaining proinsulin of the formula I ##STR2## which comprises (A) reacting a protein of the Formula II,

• R.sup.2 -R.sup.1 -B2-B29-Y-X-Gly-A2-A20-R.sup.3 (II)
• with a quantity of a mercaptan, which quantity yields 2 to 10 --SH radicals of the mercaptan per cysteine residue of the protein of the Formula II, in the presence of at least one chaotropic auxiliary agent in an aqueous medium at a pH of 10 to 11 and at a concentration of the protein of the Formula II of 0.05 to 0.3 g per liter of aqueous medium, and the to form a reaction mixture;
• (B) mixing the reaction mixture with 3 to 50 g of a hydrophobic adsorber resin per liter of aqueous medium at a pH of 4 to 7, to form the proinsulin of the Formula I;
• (C) isolating the adsorber resin, which has adsorbed proinsulin of the Formula I;
• and
• (D) desorbing the proinsulin of the Formula I from the adsorber resin;
• wherein in Formula I and II
• X is a) a genetically encodable amino acid residue or b) a peptide having 2 to 35 amino acid residues,
• Y is a genetically encodable amino acid residue,
• R.sup.1 is a phenylalanine residue or a covalent bond,
• R.sup.2 is a) a hydrogen atom, b) a genetically encodable amino acid residue or c) a peptide having 2 to 45 amino acid residues,
• R.sup.3 is a genetically encodable amino acid residue, and
• the residues A2-A20 correspond to the amino acid sequence of the A chain of human insulin, and the residues B2-B29 correspond to the amino acid sequence of the B chain of human insulin.