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Int. J. Mol. Sci. 2018, 19(2), 288;

Role of Disulfide Bonds in Activity and Stability of Tigerinin-1R

Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun 130012, China
College of Life Sciences, Jilin University, Changchun 130012, China
Author to whom correspondence should be addressed.
Received: 12 December 2017 / Revised: 12 January 2018 / Accepted: 17 January 2018 / Published: 23 January 2018
(This article belongs to the Section Biochemistry)
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Tigerinin-1R (Arg–Val–Cys–Ser–Ala–Ile–Pro–Leu–Pro–Ile–Cys–His–NH2), a cationic 12-mer peptide containing a disulfide bond extracted from frog skin secretions, lacks antibacterial activity, but has the ability to stimulate insulin release both in vitro and in vivo. To study the structure–function relationships of tigerinin-1R, we designed and synthesized five analogs, including tigerinin-cyclic, tigerinin-1R-L4, tigerinin-linear, [C3K]tigerinin-1R, and [C11K]tigerinin-1R. Tigerinin-1R promoted insulin secretion in a concentration-dependent manner in INS-1 cells without obvious cytotoxicity. At a concentration of 10−5 M, [C11K]tigerinin-1R exhibited the highest stimulation ability, suggesting that the positive charge at the C-terminus may contribute to the in vitro insulin-releasing activity of tigerinin-1R. Tigerinin-1R peptides stimulated insulin release in INS-1 cells through a universal mechanism that involves mobilization of intracellular calcium without disrupting the cell membrane. In vivo experiments showed that both tigerinin-1R and [C11K]tigerinin-1R improved glucose tolerance in overnight-fasted mice. Due to its structural stability, tigerinin-1R showed superior hypoglycemic activity to [C11K]tigerinin-1R, which suggested a critical role of the disulfide bonds. In addition, we also identified a protective effect of tigerinin-1R peptides in apoptosis induced by oxidative stress. These results further confirm the potential for the development of tigerinin-1R as an anti-diabetic therapeutic agent in clinical practice. View Full-Text
Keywords: tigerinin-1R; INS-1; Ca2+ influx; disulfide bonds; oxidative stress tigerinin-1R; INS-1; Ca2+ influx; disulfide bonds; oxidative stress

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Chen, X.; Hu, C.; Huang, Y.; Chen, Y. Role of Disulfide Bonds in Activity and Stability of Tigerinin-1R. Int. J. Mol. Sci. 2018, 19, 288.

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