Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Covalently linked insulin dimers have been prepared by cross-linking two insulin monomers with a flexible suberoyl chain at either the B1 phenylalanine or the B29 lysine residue. Binding potencies of dimers determined by inhibition of binding of 125I-insulin to isolated rat liver plasma membranes or adipocytes were 2.5-7-fold greater than their abilities to stimulate lipogenesis in adipocytes. Rates of liver plasma-membrane-associated degradation of labelled insulin and dimers, measured by gel filtration, were similar at 37 degrees C. Binding and lipogenesis potencies of dimers prepared by substitution of each monomeric half of an asymmetrical dimer with desoctapeptide insulin, an almost inactive derivative, implicated the B1-cross-linked monomeric half as predominantly interacting with the insulin receptor. These results suggest that (1) dimers bind univalently to a bivalent insulin-receptor complex, in which the two individual binding subunits are arranged with anti-parallel symmetry and (2) the mechanism by which insulin binds and initiates its biological responses requires a conformational change within the insulin-receptor complex and/or in the insulin molecule for full biological expression.
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PMID:Evidence concerning the mechanism of insulin-receptor interaction and the structure of the insulin receptor from biological properties of covalently linked insulin dimers. 636 79

The synthesis of six isomeric insulin dimers, linked through selected amino groups of the monomers by a dicarboxylic acid, is described. Symmetrical dimers were obtained by direct crosslinking of N,N-bis(methylsulfonyl-ethoxycarbonyl)insulins with the bis(p-nitrophenyl) esters of dicarboxylic acids. The synthesis of asymmetrical dimers was achieved by use of Msc-protected insulin active ester intermediates. N epsilon-B29,N epsilon B29'-Insulin dimers containing oxalyl, suberoyl and dodecanedioyl crosslinks were produced. N alpha B1,N epsilon B29'-Insulin dimers were suberoyl and dodecanedioyl crosslinks were synthesized; all other dimers were synthesized with suberoyl crosslinks. The positions of crosslinks were determined by sulfitolysis, tryptic digestion, electrophoresis and quantitative end-group determination. The dimers showed potencies between 1-60% that of insulin on a weight basis in stimulating lipogenesis in isolated fat cells. The potencies are considerably lower than the relative binding affinities determined with isolated fat cells.
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PMID:Preparation and properties of covalently linked insulin dimers. 704 9