CHEMICAL DERIVATION OF HUMAN INSULIN SUPERAGONISM |
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Authors: | MA Baoquan KANG Wei YAN Junkai |
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Institution: | 1. Key Laboratory for Functional Polymer Material of Ministry of Education, The College of Life Science Nankai University, Tianjin 300071, China 2. Tianjin Vocational Technical college of Biological Engineering, Tianjin 300462, China |
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Abstract: | The role of three highly conserved insulin residues TyrB26 was studied to better understand the relationship between insulin and receptor from rat adipose tissue plasma membranes. Insulin analogues with a single amino acid substitution or single N-methylation of the peptide bond in the position B26 were all shortened in the C-terminus of the B-chain by four amino acids. The effect of modifications was followed by the binding to the insulin receptor. From our results, we can deduce several conclusions: (1) the replacement of tyrosine in the position B26 by histidine,N-MeHisB26]-des-tetrapeptide-(B27~B30)-insulin-B26-amide and N-MeGluB26]-des-tetrapeptide(B27~B30)-insulin-B26-amide, have no significant effect on the binding affinity and they show binding affinity 105%, 190% and 208%, respectively, of that of human insulin; (2) AadB26]-des-tetrapeptide-(B27~B30)-insulin-B26-amide and Phe(4-carboxyB26)]-des-tetrapeptide(B27~B30)-insulin-B26-amide affect the potency highly positively in vitro studies; they show binding affinity 529 and 289 %, respectively, of that of human insulin. |
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Keywords: | Insulin Binding affinity [N-MeHisB26]-des-tetrapeptide-(B27~B30)-insulin-B26-amide |
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