ISSN:
1573-4943
Keywords:
insulin analogues
;
insulin-like growth factor
;
peptide synthesis
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract A modified insulin, in which the A chain moiety has been extended at the C-terminus with the “D region” of the insulin-like growth factor II, has been synthesized essentially by the procedures employed in this laboratory for the synthesis of insulin and analogues. This hybrid molecule displayed reduced insulin-like activities, 34.5% receptor binding, and 40.4% stimulation of lipogenesis relative to natural insulin. These findings suggest that the extension sequence (“D region”) attached at the C-terminus of the A chain may partially cover the putative receptor binding region of insulin, in support of speculations based on computer-generated models. These same models indicate that the extension peptide may interfere with one of the two regions implicated in insulin antibody recognition. In this regard, radioimmunoassay of the hybrid revealed potency even more reduced than biological activity: 18% relative to insulin. Growth factor assays of the hybrid (this laboratory, unpublished data) suggest that the “D region” of insulin-like growth factor II is not in itself the determinant of growth-promoting activity.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01025170
