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Information Journal Paper

Title

Construction of a single domain antibody against the receptor binding domain of VEGF with the ability of binding to its critical functional region

Pages

  0-0

Keywords

Vascular endothelial growth factor (VEGF)Q2
Single domain antibody (VHH)Q2

Abstract

 Regarding the importance of inhibiting VEGF and unique features of VHHs as a new generation of antibody-based therapeutics, the present study aimed to generate VHHs against the receptor binding domain of VEGF, thereby blocking of VEGF binding to its receptor. After preparing the gene repertoire of VHH fragments from an immunized camel, a VHH phage display library was constructed. We adopted a stringent successive biopanning to isolate the phages displaying VHH with high affinity to VEGF-RBD. A significant enrichment of phages that specifically bound to the target protein was obtained after six rounds of panning. Of the specific clones with high binding affinity screened by monoclonal phage ELISA, 52% shared the same VHH sequence, showing its high enrichment. Using molecular simulation of antigen-antibody interaction based on the crystallographic information of VEGF/VEGFR2, molecular dynamics simulations and MM/PBSA free energy calculations, we provide a reliable picture of the binding site of antibody on antigen. The key residues in the VEvhh1-VEGF interface were dissected and the energetics was analyzed by MM/PBSA. The results of studies revealed that VEvhh1 binds to the receptor binding site of VEGF with high binding energy and showed the highest affinity to the residues of VEGF which are responsible for VEGF binding to VEGFR2. Also the antibody potently covers these key functional residues of VEGF, thereby inhibiting VEGF binding to its receptor and probably abrogating its biological activity. This study may represent VEvhh1 as an anti-VEGF and anti-angiogenic candidate.

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  • Cite

    APA: Copy

    SHAHANGIAN, SEYEDEH SHIRIN, JALILI, SHIRIN, MOHSENI, AMMAR, HASSAN SAJEDI, REZA, HASANNIA, SADEGH, TAGHDIR, MAJID, MOHAMMADI, MOHAMMAD, & Sariri, Rayhaneh. (2014). Construction of a single domain antibody against the receptor binding domain of VEGF with the ability of binding to its critical functional region. JOURNAL OF BIOTECHNOLOGY, 5(1 ), 0-0. SID. https://sid.ir/paper/366026/en

    Vancouver: Copy

    SHAHANGIAN SEYEDEH SHIRIN, JALILI SHIRIN, MOHSENI AMMAR, HASSAN SAJEDI REZA, HASANNIA SADEGH, TAGHDIR MAJID, MOHAMMADI MOHAMMAD, Sariri Rayhaneh. Construction of a single domain antibody against the receptor binding domain of VEGF with the ability of binding to its critical functional region. JOURNAL OF BIOTECHNOLOGY[Internet]. 2014;5(1 ):0-0. Available from: https://sid.ir/paper/366026/en

    IEEE: Copy

    SEYEDEH SHIRIN SHAHANGIAN, SHIRIN JALILI, AMMAR MOHSENI, REZA HASSAN SAJEDI, SADEGH HASANNIA, MAJID TAGHDIR, MOHAMMAD MOHAMMADI, and Rayhaneh Sariri, “Construction of a single domain antibody against the receptor binding domain of VEGF with the ability of binding to its critical functional region,” JOURNAL OF BIOTECHNOLOGY, vol. 5, no. 1 , pp. 0–0, 2014, [Online]. Available: https://sid.ir/paper/366026/en

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