Abstract
To overcome the lack of in vivo stability of certain peptides used in cancer treatment and to increase their retention time in the extracellular matrix of the target tissue, the anti-angiogenic WHLPFKC sequence is synthesised at the uppermost branching generation of a poly(ε-lysine) dendron. The root of these dendrons is designed to interact preferentially with macromolecules of the extracellular matrix, whilst the uppermost branching generation of the dendron increased the exposed density of the bioactive peptide. Bioactivity testing of the blockers is performed on HUVECs. The results show that the dendron tethered with VEGF blockers was still able to inhibit proliferation and angiogenesis. Their relatively larger structure did not prevent the interaction with VEGF.
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Angiogenesis Inhibitors / chemical synthesis
-
Angiogenesis Inhibitors / pharmacology*
-
Anthracenes / chemical synthesis
-
Anthracenes / pharmacology*
-
Cell Proliferation / drug effects
-
Cell Survival / drug effects
-
Collagen / chemistry
-
Drug Combinations
-
Endothelium, Vascular / drug effects*
-
Endothelium, Vascular / pathology
-
Extracellular Matrix / metabolism
-
Human Umbilical Vein Endothelial Cells
-
Humans
-
Laminin / chemistry
-
Neovascularization, Pathologic / prevention & control*
-
Peptides / chemical synthesis
-
Peptides / pharmacology*
-
Polylysine / chemistry
-
Proteoglycans / chemistry
-
Solid-Phase Synthesis Techniques
-
Vascular Endothelial Growth Factor A / antagonists & inhibitors*
-
Vascular Endothelial Growth Factor A / metabolism
Substances
-
Angiogenesis Inhibitors
-
Anthracenes
-
Drug Combinations
-
Laminin
-
Peptides
-
Proteoglycans
-
Vascular Endothelial Growth Factor A
-
dendron
-
matrigel
-
Polylysine
-
Collagen