期刊
DRUG DELIVERY
卷 19, 期 4, 页码 202-207出版社
INFORMA HEALTHCARE
DOI: 10.3109/10717544.2012.690004
关键词
Protein engineering; angiogenesis; erythropoietin; PLGF-2; heparin-binding proteins
资金
- Ministry of Education in Japan [21590887, 19590856, 21590888, 18590806]
- Grants-in-Aid for Scientific Research [21590887, 19590856, 21590888, 18590806] Funding Source: KAKEN
To synthesize long-acting and antiangiogenic erythropoietin to be clinically applied for treatment of patients with solid tumors, we synthesized a hybrid molecule of human erythropoietin added onto the C-terminus with a heparin-binding motif of human PLGF-2 to develop a novel derivative of long-acting and antiangiogenic erythropoietin: heparin-binding erythropoietin (HEPO), and studied the characteristics of this novel erythropoietin derivative. HEPO cDNA was synthesized, expressed in insect cells, and the protein was purified using a heparin-sepharose affinity column. The erythropoietic and angiogenic effects of the partially purified protein were analyzed in vitro and in vivo. The erythropoietic activity of the protein was equivalent to natural EPO in vitro. In vivo administration of the protein to mice revealed its long-acting erythropoietic activity as expected. Administration of the protein inhibited angiogenesis in a mouse limb ischemia model. In conclusion, the heparin-binding motif of PLGF-2 may act as, so to speak, a superendostatin. This novel long-acting erythropoietin derivative may have an advantage to inhibit tumor growth while preserving hematopoietic and tissue-protective effects.
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