Synthesis of a biologically active truncated insulin. Des(pentapeptide B26–30) human (porcine) insulin

Abstract

An analogue of human (porcine) insulin which differs from the parent molecule in that the C-terminal pentapeptide sequence of the B chain has been eliminated has been synthesized. For this purpose, des(pentapeptide B^26–30) B chain S-sulphonate was synthesized by the fragment condensation approach and isolated in highly purified form. Interaction of this compound with the thiol form of the A chain of human (porcine) insulin yielded des(p entapeptide B^26–30) human (porcine) insulin, which was purified by chromatography on a carboxymethylcellulose column with an exponential sodium chloride gradient. The des(pentapeptide B^26–30) insulin shows potencies of 8·5–9 I.U. mg^–1 when assayed by the mouse convulsion method and of 11 I.U. mg^–1 by the radioimmunoassy method (cf. 23–25 I.U. mg^–1 for the natural hormone). This indicates that the C-terminal pentapetide sequence of the B chain does not participate functionally in the mechanism of the action of insulin.