期刊
CARBOHYDRATE POLYMERS
卷 207, 期 -, 页码 79-90出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2018.11.043
关键词
Glycol-split heparin; ES2; Anti-angiogenesis; Zebra fish; Stability
资金
- National Natural Science Foundation of China [81473129]
- Shandong Provincial Key Research and Development Program [2015GSF118099]
- Shandong Provincial Natural Science Foundation [ZR2015HM043]
- Fundamental Research Funds of Shandong University [2014JC044]
Endostatin (ES) has attracted considerable attention for the treatment of anti-angiogenesis-related disorders. An 11-amino-acid peptide (ES2, IVRRADRAAVP) from the amino terminal of ES is of interest because it is the main active fragment of ES. However, both ES and ES2 have a poor stability and a short half-life, and other disadvantages need to be further resolved. Thus, we conjugated ES2 to glycol-split heparin derivatives (GSHPs) to yield the polymer-peptide conjugate, GSHP-ES2. This study showed that GSHP-ES2 exhibited increased stability, a wider pH activity range, better inhibition of endothelial cell proliferation, migration and tube formation in vitro, better anti-angiogenic activity and a longer half-life in vivo compared with ES2. These results also indicate that GSHP-ES2 has good potential for the treatment of angiogenesis-related diseases, either alone or in combination with other chemicals.
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