Method for producing chimeric polypeptides

A method for producing a chimeric polypeptide having two polypeptide chains that are linked to each other by 1 to 3 cysteine-based disulfide bridges, which comprises:

• (a) providing a first polypeptide chain that consists essentially of from 1 to 3 cysteines and from 4 to 12 basic amino acids selected from the group consisting of arginine, lysine, and ornithine, the first polypeptide having attached to its C- or N-terminus a first biologically active compound;
• (b) providing a second polypeptide chain that consists essentially of 1 to 3 cysteines and 4 to 12 acidic amino acids selected from the group consisting of glutamate and aspartate, the second polypeptide having attached to its C- or N-terminus a second biologically active compound;
• (c) bringing the first polypeptide chain into spacial proximity with the second polypeptide chain under conditions such that the basic amino acids on the first polypeptide chain interact ionically with the acidic amino acids on the second polypeptide chain;
• and
• (d) treating the first polypeptide chain and the second polypeptide chain that have interacted ionically with each other with an oxidizing agent under conditions such that the 1 to 3 cysteines of the the first polypeptide chain form disulfide bridges with the 1 to 3 cysteines of the second polypeptide chain to produce the chimeric polypeptide.