کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10750116 | 1050296 | 2015 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Selection and characterization of human PCSK9 antibody from phage displayed antibody library
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Selection and characterization of human PCSK9 antibody from phage displayed antibody library Selection and characterization of human PCSK9 antibody from phage displayed antibody library](/preview/png/10750116.png)
چکیده انگلیسی
Proprotein convertase subtilisin/kexin type 9 (PCSK9), which involves in low-density lipoprotein cholesterol (LDL-C) metabolism by interacting with the LDL receptor, is considered as a potent therapeutic target for treating hypercholesterolemia. Here, a fab antibody phage display library was constructed and employed for bio-panning against recombinant PCSK9. A Fab fragment (designated PA4) bound with high affinity to PCSK9 was isolated after four rounds of panning. The fully human antibody IgG1-PA4 bound specifically to PCSK9 with nanomolar affinity. In vitro, IgG1-PA4 inhibited PCSK9 binding to LDLR and attenuated PCSK9-mediated degradation of LDLR on the HepG2 cell surface. In C57BL/6 mice, administration of IgG1-PA4 at 30 mg/kg increased hepatic LDLR protein levels by as much as 3 fold when compared with control. Taken together, these results suggested that the IgG1-PA4 can be served as a potential candidate for the treatment of hypercholesterolemia by inhibiting PCSK9-mediated degradation of cell surface LDLRs.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 463, Issue 4, 7 August 2015, Pages 712-718
Journal: Biochemical and Biophysical Research Communications - Volume 463, Issue 4, 7 August 2015, Pages 712-718
نویسندگان
Yan Cao, Huan Yang, Xiaolong Zhou, Huiwen Mao, Tingting Gao, Zhigang Hu, Lingfeng He, Feiyan Pan, Zhigang Guo,