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CHEN Chen, LI Wen, TONG Yue, YAO Wenbing. Modification of mPEGylated novel bifunctional fusion protein GAD and its propenty[J]. Journal of China Pharmaceutical University, 2017, 48(3): 355-360. DOI: 10.11665/j.issn.1000-5048.20170317
Citation: CHEN Chen, LI Wen, TONG Yue, YAO Wenbing. Modification of mPEGylated novel bifunctional fusion protein GAD and its propenty[J]. Journal of China Pharmaceutical University, 2017, 48(3): 355-360. DOI: 10.11665/j.issn.1000-5048.20170317
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Modification of mPEGylated novel bifunctional fusion protein GAD and its propenty

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  • In order to solve the difficucties of renaturation and immunogenicity of new bifunctional fusion protein GAD, inclusion bodies of GAD were modified by PEG-maleimide. Conformational changes of the modified GAD were compared by circular dichroism and tryptophan fluorescence spectroscopy. The biological activity was verified by oral glucose tolerance test and lipid scavenging. The results showed that PEG-maleimide completed the specific-point modification of GAD, and improved its refolding efficiency. The secondary and tertiary structures of mPEGylated GAD were consistent with that of GAD. PEG-GAD has significant hypoglycemic and lipid-lowering effects(P<0. 001)with longer half life in vivo and lower immunogenicity(P<0. 01). This study provides effective strategies for the development of strongly hydrophobic peptide drugs.
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  • [1]
    Holst JJ,Vilsboll T,Deacon CF.The incretin system and its role in type 2 diabetes mellitus[J].Mol Cell Endocrinol,2009,297(1/2):127-136.
    [2]
    Li C,Huan Y,Shen N,et al.A novel GLP-1 analog,BPI3006,with potent DPP IV resistance and good glucoregulatory effect[J].Biochem Biophys Res Commun,2010,400(4):563-568.
    [3]
    Lee CY. Glucagon-like peptide-1 formulation-the present and future development in diabetes treatment[J].Basic Clin Pharmacol Toxicol,2016,118(3):173-180.
    [4]
    de Boer MP,Meijer RI,Richter EA,et al.Globular adiponectin controls insulin-mediated vasoreactivity in muscle through AMPK2[J].Vascul Pharmacol,2016,78:24-35.
    [5]
    Adya R,Tan BK,Randeva HS.Differential effects of leptin and adiponectin in endothelial angiogenesis[J].J Diabetes Res,2015,doi: 10.1155/2015/648239.
    [6]
    Ge H,Xiong Y,Lemon B,et al.Generation of novel long-acting globular adiponectin molecules[J].J Mol Biol,2010,399(1):113-119.
    [7]
    Bhatti AB,Usman M.Drug targets for oxidative podocyte injury in diabetic nephropathy[J].Cureus,2015,7(12):e393.
    [8]
    Gao M,Tong Y,Li W,et al.Improving the anti-diabetic activity of GLP-1 by fusion with globular adiponectin[J].Artif Cells Nanomed Biotechnol,2013,41(3):159-164.
    [9]
    Yamaguchi S,Yamamoto E,Mannen T,et al.Protein refolding using chemical refolding additives[J].Biotechnol J,2013,8(1):17-31.
    [10]
    Cai Y,Zhang Z,Fan K,et al.Pharmacokinetics,tissue distribution,excretion,and antiviral activity of PEGylated recombinant human consensus interferon-variant in monkeys,rats and guinea pigs[J].Regul Pept,2012,173(1/2/3):74-81.
    [11]
    Gao M,Jin Y,Tong Y,et al.A site-specific PEGylated analog of exendin-4 with improved pharmacokinetics and pharmacodynamics in vivo[J].J Pharm Pharmacol,2012,64(11):1646-1653.
    [12]
    Wu J,Lu S,Zheng Z,et al.Modification with polysialic acid-PEG copolymer as a new method for improving the therapeutic efficacy of proteins[J].Prep Biochem Biotechnol,2016,46(8):788-797.
    [13]
    da-Silva-Freitas D,Boldrini-Franca J,Arantes EC.PEGylation:a successful approach to improve the biopharmaceutical potential of snake venom thrombin-like serine protease[J].Protein Pept Lett,2015,22(12):1133-1139.
    [14]
    El-Shishtawy SH,Mosbah O,Sherif N,et al.Association between serum visfatin and carotid atherosclerosis in diabetic and non-diabetic patients on maintenance hemodialysis[J].Electron Physician,2016,8(2):1966-1972.
    [15]
    Nan MH,Park JS,Myung CS.Construction of adiponectin-encoding plasmid DNA and gene therapy of non-obese type 2 diabetes mellitus[J].J Drug Target,2010,18(1):67-77.
    [16]
    Zhong J,Cai X,Liu C,et al.Purification and conformational changes of bovine PEGylated-lactoglobulin related to antigenicity[J].Food Chem,2016,199:387-392.
    [17]
    Moosmann A,Muller E,Bottinger H.Purification of PEGylated proteins,with the example of PEGylated lysozyme and PEGylated scFv[J].Methods Mol Biol,2014,1129:527-538.
    [18]
    Fee CJ,Van Alstine JM.Purification of pegylated proteins[J].Methods Biochem Anal,2011,54:339-362.
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