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Characterization, bioactivity and pharmacokinetic study of a novel carbohydrate-peptide polymer: Glycol-split heparin-endostatin2 (GSHP-ES2)

Sun, Feng, Wang, Zhendong, Yang, Zhifang, Li, Yan, Cui, Huifei, Liu, Chunhui, Gao, Dezong, Wang, Fengshan, Tan, Haining
Carbohydrate polymers 2019 v.207 pp. 79-90
amino acids, bioactive properties, cell proliferation, endothelial cells, half life, heparin, pH, pharmacokinetics, polymers
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.