摘要 |
A process for the production of insulin or an insulin analog is provided by combination of an A-chain and a B-chain, which comprises reacting the S-sulfonated form of the A-chain, the S-sulfonated form of the B-chain, and a thiol. reducing agent together in an aqueous medium under conditions which produce a mixture having (1) a pH of from about 8 to about 12, (2) a total protein concentration of from about 0.1 to about 50 milligrams per milliliter, and (3) an amount of thiol reducing agent which affords a total of from about 0.4 to about 2.5 -SH groups per each -SSO3<-> group present in the total amount of A- and B-chain S-sulfonates, and allowing formation of insulin or an insulin analog to occur by maintaining the mixture at a temperature of from about 0 DEG C. to about 25 DEG C. and in an environment which provides a source of oxygen. |