期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 19, 期 1, 页码 149-152出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2008.10.132
关键词
Ternary heparin conjugate; Drug delivery system; Anticoagulant activity
资金
- 985 Foundation of Ministry of Education
- National Natural Science Foundation of China [20472018]
- Natural Science Foundation of Hunan [07JJ3019]
- Doctoral Fund of Ministry of Education of China [20060532022]
- Department of Science and Technology of Changsha [K082152]
A model ternary heparin conjugate by direct covalent bond strategy has been developed, in which modified heparin using active mix anhydride as intermediate conjugates with model drug molecule and model specific ligand, respectively. Designed ester bonds between model drug and heparin facilitate hydrolysis kinetics research. The strategy can be extended to design and synthesize a targeted drug delivery system. The key point is to use mixed anhydride groups as activating intermediates to mediate the synthesis of the ternary heparin conjugate. Formation of mixed anhydride is detected by the conductimetry experiment. The ternary heparin conjugate is characterized by C-13 NMR, FT-IR and GPC, respectively. The decreased trend on degree of substitution (DS) is consistent with that of introduced anticancer drug and specific ligand in drug delivery system. Moreover, their anticoagulant activity is evaluated by measuring activated partial thromboplastin time (APTT) and anti-factor Xa activity. The results show that model ternary heparin conjugate with reduced anticoagulant activity may avoid the risk of severe hemorrhagic complication during the administration and is potential to develop a safe and effective drug delivery system on anticancer research. (C) 2008 Elsevier Ltd. All rights reserved.
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