A synthetic human insulin analogue modified at position B22. [Lys22-B] human insulin

Abstract

A human insulin analogue which differs from the parent molecule in that the amino-acid residue arginine at position 22 in the B chain is replaced by lysine has been synthesized. For this purpose a human B chain analogue, in which the arginine residue at position 22 was replaced by a lysine residue, was prepared by the fragment condensation approach and isolated as the S-sulphonate. Combination of the latter compound with the thiol form of the human (porcine) insulin A chain yielded the [Lys-²²B] human insulin. This analogue was isolated in highly purified form by chromatography on a carboxymethylcellulose column with an exponential sodium chloride gradient. [Lys-²²B] insulin shows potencies of 13–14 I.U. mg^–1 when assayed by the mouse convulsion method and of 8 I.U. mg^–1 by the radioimmunoassay method (cf. 23–25 I.U. mg^–1 for the natural hormone).