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Computational and in Vitro Targeting of Huvecs by Ara-Linker-Tgfαl3 Through Vegfr2 Publisher



Ghadaksaz A1 ; Imani Fooladi AA2 ; Mahmoodzadeh Hosseini H2 ; Amin M3 ; Adami Ghamsari F1
Authors

Source: Molecular Simulation Published:2024


Abstract

Angiogenesis blockade represents a therapeutic strategy to inhibit the growth of the tumour and its progression and metastasis. Targeting the vascular endothelial growth factor receptor 2 (VEGFR2) is among the approaches approved as anti-cancer drugs. In this study, we examined ARA-linker-TGFαL3 and TGFαL3 binding affinity to VEGFR2. Next, the cytotoxicity effect of ARA-linker-TGFαL3 on human umbilical vein endothelial cells was evaluated. The 100 ns molecular dynamic simulation was employed to estimate the stability of the ligand–receptor interaction and the free energy decomposition was performed by molecular mechanics generalised Born surface area method. The MTT test evaluated the proliferation inhibition of ARA-linker-TGFαL3 and arazyme on HUVECs cells. Also, the change in VEGFR2 gene expression was investigated after treatment with recombinant proteins. Analysis of the trajectory using the root-mean-square deviation and fluctuation, radius of gyration, H-bond calculation, and binding free energy showed that ARA-linker-TGFαL3 formed the more stable complex with the D2 and D3 domains of VEGFR2 than TGFαL3. Meanwhile, ARA-linker-TGFαL3 revealed higher cytotoxicity and inhibition of VEGFR2 expression than arazyme. The results of the current study suggest the anti-angiogenesis effects of ARA-linker-TGFαL3 that can be useful in cancer therapy. © 2023 Informa UK Limited, trading as Taylor & Francis Group.
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