Synthesis of an insulin-like compound consisting of the A chain of insulin and a B chain corresponding to the B domain of human insulin-like growth factor I.
An insulin-like hybrid molecule consisting of the A chain of insulin and a B chain corresponding to the B domain of human insulin-like growth factor I (growth factor I sequence 1-30) has been synthesized essentially by the procedures developed in this laboratory for the synthesis of insulin and analogues. The hybrid competed with 125I-insulin for insulin receptors in rat liver plasma membranes and was a full agonist in stimulating incorporation of [3(-3)H]glucose into lipids in rat adipocytes. In both assays, the compound displayed ca. 2% of the potency of insulin. The compound was recognized by anti-insulin antibodies but was only ca. 0.25% as potent as insulin in this activity. The hybrid exhibited growth-promoting activity in fibroblasts, displaying 3-8% of the activity of insulin. In contrast, the compound was recognized by insulin-like growth factor carrier proteins, a property not associated with insulin. Two points of nonhomology between the B chain of insulin and the B domain of insulin-like growth factor I are considered in connection with these observations.
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000138:chemical synthesis* / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000138:chemical synthesis*; D008055:Lipids / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism; D046911:Macromolecular Substances; D010446:Peptide Fragments; D055503:Protein Multimerization; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D013002:Somatomedins / Q000138:chemical synthesis*
D000596:Amino Acids; D007328:Insulin; D008055:Lipids; D046911:Macromolecular Substances; D010446:Peptide Fragments; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D011972:Receptor, Insulin