The role of the arginine-B22 residue in insulin action

Abstract
The modification of the side chain of the arginine-B22 residue of insulin by the N8N9-(1,2-dihydroxycyclohex-1,2-ylene) group and by the adipoyl group is described. These are the 1st insulin derivatives described that contain a modified arginine residue in an otherwise unaltered molecule. When tested for their ability to lower rat blood sugar concentration, both modified insulins showed a specific activity indistinguishable from that of insulin. As the substituent groups involved are very bulky and in 1 case of opposite charge to that of the side chain, the retention of biological activity casts doubt on the idea, previously generally accepted, that the arginine-B22 residue is essential to the activity of the hormone.