a better anti-diabetic recombinant human fibroblast growth factor 21 (rhfgf21) modified with polyethylene glycol更好的抗糖尿病重组人成纤维细胞生长因子21(rhfgf21)与聚乙二醇改性.pdfVIP

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2017-09-07 发布于上海
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a better anti-diabetic recombinant human fibroblast growth factor 21 (rhfgf21) modified with polyethylene glycol更好的抗糖尿病重组人成纤维细胞生长因子21(rhfgf21)与聚乙二醇改性.pdf

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a better anti-diabetic recombinant human fibroblast growth factor 21 (rhfgf21) modified with polyethylene glycol更好的抗糖尿病重组人成纤维细胞生长因子21(rhfgf21)与聚乙二醇改性

A Better Anti-Diabetic Recombinant Human Fibroblast Growth Factor 21 (rhFGF21) Modified with Polyethylene Glycol 1,2. 2. 1. 1 3 1,4 Zhifeng Huang , Huiyan Wang , Meifei Lu , Chuanchuan Sun , Xiaoping Wu , Yi Tan , Chaohui 1 1 1 1,4 1,2,3 Ye , Guanghui Zhu , Xiaojie Wang , Lu Cai *, Xiaokun Li * 1 School of Pharmacy and Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical College, Wenzhou, Zhejiang, China, 2 Normal Bethune Medical College, Jilin University, Changchun, Jilin, China, 3 Key Laboratory of Ministry of Education for Tissue Transplantation and Immunology, Jinan University, Guangzhou, Guangdong, China, 4 Department of Pediatrics, University of Louisville, Louisville, Kentucky, United States of America Abstract As one of fibroblast growth factor (FGF) family members, FGF21 has been extensively investigated for its potential as a drug candidate to combat metabolic diseases. In the present study, recombinant human FGF21 (rhFGF21) was modified with polyethylene glycol (PEGylation) in order to increase its in vivo biostabilities and therapeutic potency. At N-terminal residue rhFGF21 was site-selectively PEGylated with mPEG20 kDa-butyraldehyde. The PEGylated rhFGF21 was purified to near homogeneity by Q Sepharose anion-exchange chromatography. The general structural and biochemical features as well as anti-diabetic effects of PEGylated rhFGF21 in a type 2 diabetic rat model were evaluated. By N-terminal sequencing and MALDI-TOF mass spectrometry, we confirmed that PEG molecule was conjugated only to the N-terminus