Impaired negative cooperativity of the semisynthetic analogues human [LeuB24]- and [LeuB25]-insulins |
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Authors: | Linda M. Keefer Marie-Agnès Piron Pierre De Meyts Hans-Gregor Gattner Cornelia Diaconescu Derek Saunders Dietrich Brandenburg |
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Affiliation: | 1. International Institute of Cellular and Molecular Pathology, UCL 7529; Avenue Hippocrate, 75; B-1200 Brussels, Belgium;1. Deutsches Wollforschungsinstitut, Veltmanplatz, 8, D-5100 Aachen, West Germany. |
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Abstract: | Several semisynthetic analogues of human insulin were prepared by enzyme-assisted coupling of synthetic octapeptides to the C-terminal of porcine desoctapeptide insulin. We report the receptor-binding and biological properties of [LeuB24]- and [LeuB25]-insulins, one of which has the same sequence as a “mutant” insulin recently found in a diabetic patient (Tager, H. et al.(1979) Nature :121–125). [LeuB24]- and [LeuB25]-insulins had, respectively, 8–12% and 0.9–1.1% of the binding affinity of human insulin, and 11% and 2.7% of its potency in stimulating lipogenesis in isolated rat fat cells. Neither one was an antagonist of the biological effects of native insulin. While the ability of [LeuB24]-insulin to induce negative cooperativity was clearly impaired, that of [LeuB25]-insulin was almost abolished. [LeuB25]-insulin was also a potent antagonist of the negative cooperativity induced by native insulin. |
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Keywords: | DAA desalanine(B30)-desasparagine(A21) insulin DOP desoctapeptide (B23-30) insulin |
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