Discovery of a sulfated tetrapeptide that binds to vascular endothelial growth factor.
Molecules that mimic the sulfated glycosaminoglycan heparin and bind to heparin-binding growth factors would serve as important building blocks for synthetic biomaterials, e.g. to create a growth factor reservoir within a matrix. Peptide-based heparin mimetics would be particularly attractive, given the ease of peptide synthesis and modification. A sulfated tetrapeptide that fits this description and binds to vascular endothelial growth factor (VEGF) was discovered using a rationally-designed combinatorial approach. A approximately 6600 member library of tetrapeptides, designed to include heparin functionality, was synthesized by solid-phase Fmoc chemistry. The library was analyzed on-resin for VEGF binding using a fluorescence assay that employed a 7-amino-4-methylcoumarin-modified VEGF(165). The beads were ranked according to fluorescent signal and SY(SO(3))DY(SO(3)) was identified as the top binder. The binding affinity of the peptide for VEGF(165) was ascertained by surface plasmon resonance and compared with the heparin mimic suramin; the peptide binds to VEGF(165) 100-fold stronger than the sulfonated compound. These results suggest that the identified peptide may be useful in biomaterial applications where binding of VEGF is desired.
Maynard
Heather D
HD
Department of Materials Science and Institute for Biomedical Engineering, Swiss Federal Institute of Technology and University of Zurich, Switzerland.
Hubbell
Jeffrey A
JA
D001665:Binding Sites; D001672:Biocompatible Materials / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D009842:Oligopeptides / Q000737:chemistry*; D019151:Peptide Library; D011485:Protein Binding; D013463:Sulfuric Acid Esters / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry*
D001672:Biocompatible Materials; D009842:Oligopeptides; D019151:Peptide Library; D013463:Sulfuric Acid Esters; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A