Correlation Engine 2.0
Clear Search sequence regions


  • angiogenesis (4)
  • Flt1 (11)
  • human (3)
  • mice (1)
  • peptides (2)
  • polypeptides (5)
  • VEGF (6)
  • VEGFR1 (8)
  • Sizes of these terms reflect their relevance to your search.

    Genetically engineered fusion polypeptides have been investigated to introduce unique bio-functionality and improve some therapeutic activity for anti-angiogenesis. We report herein that stimuli-responsive, vascular endothelial growth factor receptor 1 (VEGFR1) targeting fusion polypeptides composed of a VEGFR1 (fms-like tyrosine kinase-1 (Flt1)) antagonist, an anti-Flt1 peptide, and a thermally responsive elastin-based polypeptide (EBP) were rationally designed at the genetic level, biosynthesized, and purified by inverse transition cycling to develop potential anti-angiogenic fusion polypeptides to treat neovascular diseases. A series of hydrophilic EBPs with different block lengths were fused with an anti-Flt1 peptide, forming anti-Flt1-EBPs, and the effect of EBP block length on their physicochemical properties was examined. While the anti-Flt1 peptide decreased phase-transition temperatures of anti-Flt1-EBPs, compared with EBP blocks, anti-Flt1-EBPs were soluble under physiological conditions. The anti-Flt1-EBPs dose dependently inhibited the binding of VEGFR1 against vascular endothelial growth factor (VEGF) as well as tube-like network formation of human umbilical vein endothelial cells under VEGF-triggered angiogenesis in vitro because of the specific binding between anti-Flt1-EBPs and VEGFR1. Furthermore, the anti-Flt1-EBPs suppressed laser-induced choroidal neovascularization in a wet age-related macular degeneration mouse model in vivo. Our results indicate that anti-Flt1-EBPs as VEGFR1-targeting fusion polypeptides have great potential for efficacious anti-angiogenesis to treat retinal-, corneal-, and choroidal neovascularization.

    Citation

    Min Jeong Kang, Kug-Hwan Roh, Jae Sang Lee, Jae Hee Lee, SaeGwang Park, Dong Woo Lim. Vascular Endothelial Growth Factor Receptor 1 Targeting Fusion Polypeptides with Stimuli-Responsiveness for Anti-angiogenesis. ACS applied materials & interfaces. 2023 Jul 12;15(27):32201-32214

    Expand section icon Mesh Tags

    Expand section icon Substances


    PMID: 37384534

    View Full Text