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Synthesis, characterization, and preliminary assessment of anti-Flt1 peptide–hyaluronate conjugate for the treatment of corneal neovascularization

Paper ID Volume ID Publish Year Pages File Format Full-Text
9744 644 2009 9 PDF Available
Title
Synthesis, characterization, and preliminary assessment of anti-Flt1 peptide–hyaluronate conjugate for the treatment of corneal neovascularization
Abstract

Anti-Flt1 peptide of GNQWFI has been reported to inhibit vascular endothelial growth factor receptor 1 (VEGFR1) – mediated endothelial cell migration and tube formation. In this work, a protocol to synthesize anti-Flt1 peptide–hyaluronate (HA) conjugate was successfully developed for the treatment of corneal neovascularization. Using tetrabutyl ammonium salt of HA (HA-TBA), water-insoluble anti-Flt1 peptide could be conjugated with HA in dimethyl sulfoxide (DMSO) by the amide bond formation between carboxyl groups of HA and N-terminal amine groups of GGNQWFI. The formation of anti-Flt1 peptide–HA conjugate was confirmed by 1H NMR and fluorometric analyses. The average number of grafted peptide molecules in anti-Flt1 peptide–HA conjugates could be controlled from 3 to 30 per single HA chain by changing the feeding amount of peptide for the conjugation reaction. According to in vitro biological activity tests, anti-Flt1 peptide–HA conjugate exhibited a significant inhibition effect on the binding of Flt1-Fc to VEGF165 coated on the well. Furthermore, in vivo biological activity of anti-Flt1 peptide–HA conjugate was confirmed from the inhibitory effect on corneal neovascularization in silver nitrate cauterized corneas of SD rats. The VEGF receptor 2 expression was also reduced after treatment with anti-Flt1 peptide–HA conjugate. The water-soluble anti-Flt1 peptide–HA conjugate was thought to have a potential to be developed as anti-angiogenic therapeutics for the treatment of corneal neovascularization.

Keywords
Hyaluronate; Anti-Flt1 peptide; Conjugation; Drug delivery; Corneal neovascularization
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Synthesis, characterization, and preliminary assessment of anti-Flt1 peptide–hyaluronate conjugate for the treatment of corneal neovascularization
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 30, Issue 30, October 2009, Pages 6026–6034
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us