title: Synthesis, characterisation and in vitro anti-angiogenic potential of dendron VEGF blockers.
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.
authors: Brighton Studies in Tissue Mimicry and Aided Regeneration, School of Pharmacy and Bimolecular Sciences, University of Brighton, Huxley Building, Lewes Road, Brighton, BN2 4GJ, UK.
authors: Steven T
authors: ST
authors: Meikle
authors: Valeria
authors: V
authors: Perugini
authors: Anna L
authors: AL
authors: Guildford
authors: Matteo
authors: M
authors: Santin
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D000873:Anthracenes / Q000138:chemical synthesis / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007797:Laminin / Q000737:chemistry; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D011107:Polylysine / Q000737:chemistry; D011509:Proteoglycans / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000873:Anthracenes; D004338:Drug Combinations; D007797:Laminin; D010455:Peptides; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; C501244:dendron; C059485:matrigel; D011107:Polylysine; D003094:Collagen