Effect of B22-arginine replacement on the biological activity of insulin.
The semisynthesis of a series of B23-D-Ala deshexapeptide and despentapeptide analogues with B22-arginine replaced are described. The following semisynthetic scheme is used: desnonapeptide insulin pentamethyl ester is prepared from insulin hexamethyl ester through the action of trypsin and carboxypeptidase B, the amino groups are protected with Boc-groups, the protected product is condensed with synthetic peptides, and the protecting groups are removed with trifluoroacetic acid treatment and by saponification. The biological activities of these analogues indicate that the B22-Arg is non-essential and can be replaced by Lys or even Asp without any influence on the biological activity. The activity is reduced to one half when it is replaced by valine or to a very low level when replaced by Gly or D-Arg. The reason for the low activity of guinea pig insulin is discussed.
D000818:Animals; D001120:Arginine / Q000032:analysis; D006168:Guinea Pigs; D007328:Insulin / Q000032:analysis / Q000494:pharmacology*; D051379:Mice; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship
D007328:Insulin; D010455:Peptides; D001120:Arginine