Abstract
Dopamine has previously been shown to inhibit angiogenesis in vitro and in vivo, but its clinical applications in this context are severely limited by its short half-life. Here we report the synthesis of a polyglutamic acid-dopamine conjugate and show that conjugation significantly extends (from 1 to 24 h) dopamine's antiangiogenic activity in vitro and in vivo. These findings form the basis for the development of a new class of agents for the treatment of angiogenesis-dependent diseases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inhibitors / chemical synthesis*
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Angiogenesis Inhibitors / chemistry
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Angiogenesis Inhibitors / pharmacology
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Animals
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Capillary Permeability / drug effects
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Cell Movement
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Dopamine / chemical synthesis*
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Dopamine / chemistry
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Dopamine / pharmacology
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Endothelial Cells / drug effects
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Endothelial Cells / physiology
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Female
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Humans
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In Vitro Techniques
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Mice
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Mice, Inbred BALB C
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Microvessels / drug effects
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Microvessels / physiology
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Neovascularization, Physiologic / drug effects
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Polyglutamic Acid / chemistry*
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Structure-Activity Relationship
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Umbilical Veins / cytology
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Vascular Endothelial Growth Factor A / pharmacology
Substances
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Angiogenesis Inhibitors
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Vascular Endothelial Growth Factor A
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Polyglutamic Acid
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Dopamine