A novel synthetic derivative of human erythropoietin designed to bind to glycosaminoglycans.
|
| Abstract |
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.
|
|---|---|
| Authors | Masato Moriyama, Ken Toba, Haruo Hanawa, Kiminori Kato, Takao Yanagawa, Tsugumi Takayama, Takuya Ozawa, Hironori Kobayashi, Masato Higuchi, Hideki Saito, Yoshifusa Aizawa |
| Journal | Drug delivery (Drug Deliv) Vol. 19 Issue 4 Pg. 202-7 (May 2012) ISSN: 1521-0464 [Electronic] England |
| PMID | 22643054 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!