Nature of the B10 amino acid residue. Requirements for high biological activity of insulin.
Human [10-asparagine-B] insulin ([ Asn10 -B] insulin), an analogue which differs from the parent molecule in that the histidine residue at position 10 of the B chain (B10) is replaced by asparagine, has been synthesized and isolated in purified form. In vitro biological assays indicated a potency of ca. 35% compared to insulin. We have previously shown that the replacement of histidine at position B10 by lysine resulted in an analogue displaying ca. 15% of the biological activity of natural hormone, while the substitution of leucine in this position produced a molecule exhibiting ca. 45% potency in in vivo assays. The data indicate that molecular size of the amino acid residue at position B10 may be important in the maintenance of a structure commensurate with high biological activity. Polarity at this position appears to be rather unimportant while a strongly basic group appears to be deleterious.
D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D006639:Histidine / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives* / Q000032:analysis* / Q000138:chemical synthesis / Q000494:pharmacology; D008055:Lipids / Q000096:biosynthesis; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D013329:Structure-Activity Relationship; D013552:Swine
D007328:Insulin; D008055:Lipids; D006639:Histidine; C041647:insulin, Asn(B10)-; D011972:Receptor, Insulin; D005947:Glucose