natural form of noncytolytic flexible human fc as a long-acting carrier of agonistic ligand, erythropoietin自然noncytolytic形式灵活的人类fc长效论争的配体的载体,促红细胞生成素.pdfVIP
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natural form of noncytolytic flexible human fc as a long-acting carrier of agonistic ligand, erythropoietin自然noncytolytic形式灵活的人类fc长效论争的配体的载体,促红细胞生成素
Natural Form of Noncytolytic Flexible Human Fc as a Long-Acting Carrier of Agonistic Ligand, Erythropoietin 1 2 2 1 2 2 Se Jin Im , Sang In Yang , Se Hwan Yang , Dong Hoon Choi , So Young Choi , Hea Sook Kim , Do Soo 2 3 4 4 4 4 Jang , Kyeong Sik Jin , Yo-Kyung Chung , Seung-Hee Kim , Sang Hoon Paik , Yoo Chang Park , Moon 5 5 5 1 1,2 Koo Chung , Yong Bum Kim , Kang-Hyun Han , Kwan Yong Choi , Young Chul Sung * 1 Division of Molecular and Life Sciences, POSTECH, Pohang, Republic of Korea, 2 Research Institute, Genexine Co., Seongnam, Republic of Korea, 3 Pohang Accelerator Laboratory, POSTECH, Pohang, Republic of Korea, 4 Central Research Institute, Green Cross Co., Yongin, Republic of Korea, 5 Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, Daejon, Republic of Korea Abstract Human IgG1 Fc has been widely used as a bioconjugate, but exhibits shortcomings, such as antibody- and comple- ment-mediated cytotoxicity as well as decreased bioactivity, when applied to agonistic proteins. Here, we constructed a nonimmunogenic, noncytolytic and flexible hybrid Fc (hyFc) consisting of IgD and IgG4, and tested its function using erythropoietin (EPO) conjugate, EPO-hyFc. Despite low amino acid homology (20.5%) between IgD Fc and IgG4 Fc, EPO- hyFc retained ‘‘Y-shaped’’ structure and repeated intravenous administrations of EPO-hyFc into monkeys did not generate EPO-hyFc-specific antib
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