[12-Homoarginine]glucagon: synthesis and observations on conformation,biological activity,and copper-mediated peptide cleavage |
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| Affiliation: | 1. State Key Laboratory of Supramolecular Structure and Materials, Institute of Theoretical Chemistry, Jilin University, Changchun 130012, China;2. Department of Thoracic Surgery, China-Japan Union Hospital, Jilin University, Changchun 130033, China;1. State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China;2. Department of Chemistry, Lanzhou University, Lanzhou 730000, China;3. Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Lanzhou 730000, China;4. Key Laboratory of Sensor and Sensor Technology of Gansu Province, Lanzhou 730000, China;5. Institute of Sensor Technology, Gansu Academy of Sciences, Lanzhou 730000, China;1. Department of Electrical and Electronic Engineering, Rajshahi University of Engineering & Technology, Rajshahi-6204, Bangladesh;2. Department of Biomedical Engineering, Bangladesh University of Engineering & Technology, Rajshahi-6204, Rajshahi-6204, Bangladesh;3. Department of Electronics and Telecommunication Engineering,Rajshahi University of Engineering & Technology, Rajshahi-6204, Bangladesh;1. Jiangxi Key Laboratory of Organic Chemistry, College of Chemistry and Chemical Engineering, Jiangxi Science and Technology Normal University, Nanchang, 330013, PR China;2. Department of Ecology and Environment, Yuzhang Normal University, Nanchang, 330103, PR China |
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| Abstract: | ![]()
Specific modification of the single lysine residue (Lys-12) in glucagon with O-methylisourea has been effected by blocking the reactivity of the amino terminal histidine with copper, providing a method for obtaining [12-homoarginine]glucagon. It was found that as a side reaction, under the conditions of the modification reaction, Cu(II) catalyzed cleavage of the polypeptide chain between Asp-9 and Tyr-10, and between Lys-12 and Tyr-13. This observation may be of value for development of a sequence-specific peptide cleavage procedure. The dilute solution conformations of glucagon and [12-homoarginine]-glucagon were compared by circular dichroism, fluorescence, phosphorescence, energy transfer, and optical detection of magnetic resonance. The results indicate that conversion of Lys-12 to homoarginine does not alter the helix content, the side chain conformation in the vicinity of the tyrosine and tryptophan residues, or the relative distances and orientations between these residues. However, the modification reduces the hormone potency towards activation of lipolysis in isolated rat epididymal fat cells by a factor of seven. We attribute the loss of potency to an interference with a specific interaction between the lysine residue and the fat cell hormone receptor, and not to a change in the solution conformation of the hormone. |
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