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Sci Rep. 2019 Feb 27;9(1):2978. doi: 10.1038/s41598-019-39776-0.

Enhancing bioactivity, physicochemical, and pharmacokinetic properties of a nano-sized, anti-VEGFR2 Adnectin, through PASylation technology.

Author information

1
Department of Nanobiotechnology, New Technologies Research Group, Pasteur Institute of Iran, Tehran, Iran.
2
Department of Nanobiotechnology, New Technologies Research Group, Pasteur Institute of Iran, Tehran, Iran. cohan_r@yahoo.com.
3
Department of Nanobiotechnology, New Technologies Research Group, Pasteur Institute of Iran, Tehran, Iran. dnsa@pasteur.ac.ir.
4
Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
5
Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran.
6
Department of Biotechnology, Pasteur Institute of Iran, Tehran, Iran.
7
Isfahan Cardiovascular research center, Department of Pharmacology, Isfahan, Iran.

Abstract

The crucial role of VEGF receptor 2 (VEGFR2) signaling in the angiogenesis and metastasis of solid tumors has prompted the development of inhibitors with minimal bystander effects. Recently, Adnectin C has attracted attention for cancer treatment. To overcome the problematic properties of Adnectin, a novel form of Adnectin C has been designed by its fusion to a biodegradable polymeric peptide containing Pro/Ala/Ser (PAS) repetitive residues. E. coli-expressed recombinant fused and unfused proteins were compared in terms of bioactivity, physicochemical, and pharmacokinetic properties using standard methods. Dynamic light scattering (DLS) analysis of PASylated adnectin C revealed an approximate 2-fold increase in particle size with a slight change in the net charge. Additionally, fusion of the PAS sequence improved its stability against the growth of thermo-induced aggregated forms. The high receptor-binding and improved binding kinetic parameters of PASylated Adnectin C was confirmed by ELISA and surface plasmon resonance assays, respectively. Pharmacokinetic studies showed a noticeable increase in the terminal half-life of Adnectin C-PAS#1(200) by a factor of 4.57 after single dose by intravenous injection into female BALB/c mice. The results suggest that PASylation could offer a superior delivery strategy for developing Adnectin-derived drugs with improved patient compliance.

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