Novel Vascular Endothelial Growth Factor Mimetics as Inhibitors or Activators of Angiogenesis

Tech ID: 21B159

Advantages:

  • Novel helical VEGF mimicking peptides that can inhibit or activate angiogenesis.
  • Mimetics hold promise as therapeutic agents for intervention in angiogenesis-related diseases.
  • The sulfono-γ-AA peptides exhibit remarkable stability against proteolytic hydrolysis, ensuring their durability and effectiveness in biological systems.

Summary:

Angiogenesis, the process of new blood vessel formation, while crucial for early development and healing is also a hallmark of cancer cell, promoting tumor vascular proliferation and metastasis. Many therapeutics haven been developed that inhibit angiogenesis signaling, specifically the binding of vascular endothelial growth factor-A (VEGF-A) to VEGF receptors (VEGFR). However, the efficacy of these inhibitors varies across different types of cancers, hence there is a need for more effective approaches to modulate angiogenesis.

Our researchers developed sulfono-γ-AA peptides based helical foldamers to mimic a critical binding domain on VEGF-A (helix α1). In vitro angiogenesis assays revealed that the mimetic called V3 potently inhibited angiogenesis, whereas V2 activated angiogenesis. These molecules thus can regulate proangiogenic and antiangiogenic effects and provide a key to switch maintain a biological balance in angiogenic signaling. Moreover, these helical mimetics exhibit remarkable proteolytic stability, suggesting that V2 and V3 are promising therapeutic agents for the intervention of disease conditions arising due to angiogenic imbalances and could also be used as novel molecular switching probes to interrogate the mechanism of VEGFR signaling.

 

Capillary tube formation of HUVECs following treatment with VEGF mimetics in the presence of VEGEF. A&B) Increased capillary tube formation  in cells treated with V2 and QK. C&D) Decreased capillary tube formation in cells treated with V1 and V3.

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