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

Highlights • The carboxyl group of the GSHP was linked to the amino group of the ES2 C-terminal. • The GSHP-ES2 displayed no significant anticoagulant activity. • Improved heat stability and higher P-selectin affinity was obtained through the conjugation of GSHP to ES2. • Better bioactivities of GSHP-ES2 were obtained both in vitro and in vivo. • GSHP has good potential as protein/peptide modifier. Abstract 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. [ABSTRACT FROM AUTHOR]