ArticleScientific reports2014
Simultaneous targeting of two ligand-binding sites on VEGFR2 using biparatopic Affibody molecules results in dramatically improved affinity.
Article in Scientific reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- Injection of Affibodies by a Self-Organizing Bacterial Syringe to Interfere with Intracellular Signaling.Toxins · 2025Article
- PRELP functions via multiple interactions with intrinsically weak affinity relying on ECM anchoring and remodeling.Scientific reports · 2025Article
- Surface-engineered bacteria in drug development.Microbial biotechnology · 2024Review
- Development of novel humanized VHH synthetic libraries based on physicochemical analyses.Scientific reports · 2024Article
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- An anti-sortilin affibody-peptide fusion inhibits sortilin-mediated progranulin degradation.Frontiers in immunology · 2024Article
- Ex silico engineering of cystine-dense peptides yielding a potent bispecific T cell engager.Science translational medicine · 2022Article
- Engineering mono- and multi-valent inhibitors on a modular scaffold.Chemical science · 2021Article
- Increasing thermal stability and improving biodistribution of VEGFR2-binding affibody molecules by a combination of in silico and directed evolution approaches.Scientific reports · 2020Article
- [EJNMMI research · 2020Article
- Article
- Miniproteins as a Powerful Modality in Drug Development.Trends in biochemical sciences · 2020Review
- Generation of biparatopic antibody through two-step targeting of fragment antibodies on antigen using SpyTag and SpyCatcher.Biotechnology reports (Amsterdam, Netherlands) · 2020Article
- Radionuclide imaging of VEGFR2 in glioma vasculature using biparatopic affibody conjugate: proof-of-principle in a murine model.Theranostics · 2018Article
- Staphylococcus carnosus: from starter culture to protein engineering platform.Applied microbiology and biotechnology · 2017Review
- Article
- Affibody molecules as engineered protein drugs.Experimental & molecular medicine · 2017Review
- Novel affinity binders for neutralization of vascular endothelial growth factor (VEGF) signaling.Cellular and molecular life sciences : CMLS · 2016Article
- Selecting Targets for Tumor Imaging: An Overview of Cancer-Associated Membrane Proteins.Biomarkers in cancer · 2016Review
- A 45-Amino-Acid Scaffold Mined from the PDB for High-Affinity Ligand Engineering.Chemistry & biology · 2015Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Angiogenesis plays an important role in cancer and ophthalmic disorders such as age-related macular degeneration and diabetic retinopathy. The vascular endothelial growth factor (VEGF) family and corresponding receptors are regulators of angiogenesis and have been much investigated as therapeutic targets. The aim of this work was to generate antagonistic VEGFR2-specific affinity proteins having adjustable pharmacokinetic properties allowing for either therapy or molecular imaging. Two antagonistic Affibody molecules that were cross-reactive for human and murine VEGFR2 were selected by phage and bacterial display. Surprisingly, although both binders independently blocked VEGF-A binding, competition assays revealed interaction with non-overlapping epitopes on the receptor. Biparatopic molecules, comprising the two Affibody domains, were hence engineered to potentially increase affinity even further through avidity. Moreover, an albumin-binding domain was included for half-life extension in future in vivo experiments. The best-performing of the biparatopic constructs demonstrated up to 180-fold slower dissociation than the monomers. The new Affibody constructs were also able to specifically target VEGFR2 on human cells, while simultaneously binding to albumin, as well as inhibit VEGF-induced signaling. In summary, we have generated small antagonistic biparatopic Affibody molecules with high affinity for VEGFR2, which have potential for both future therapeutic and diagnostic purposes in angiogenesis-related diseases.
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