Construction of a complex stimulator of angiogenesis based on the fusion protein ANGPT1_VEGF165
https://doi.org/10.29235/1561-8331-2026-62-1-57-70
Abstract
The proteins VEGF165 and ANGPT1 are key regulators of angiogenesis, which underpins therapeutic approaches for chronic lower-extremity ischemia. Designing a fusion protein based on these molecules has the potential to significantly enhance the therapeutic effect. To determine the optimal arrangement of functional domains of the fusion protein (VEGF165_ANGPT1 or ANGPT1_VEGF165) and establish the ideal length and sequence of the peptide linker between the two proteins, we performed an analysis of molecular dynamics trajectories and spatial structures of 134 fusion proteins. The optimal linkers that contribute to the increased stability of the fusion proteins were identified as follows: for ANGPT1_VEGF165, the optimal linkers are GGGSGGGGSGGGSGGGS, GGGGSGGGGSGGGGS, GGGSGGGGS, and PAPAPAP; for VEGF165_ ANGPT1, the optimal linkers are GGGGSGGGGGS, GGGSGGGGSGGGGSGGGS, and GGGGSGGGGSGGGGSGGGGS.
Based on the results, we selected the variant of the ANGPT1_VEGF165 protein with the GGGSGGGGSGGGSGGGS linker to analyze its functional activity.
Supporting agencies: The study was financially supported by the National Academy of Sciences of Belarus, as part of a separate project “Development of new angiogenesis modulators based on circular DNA in order to create promising gene therapy agents for the treatment of limb ischemia” (2022–2024).
About the Authors
A. B. Sachanka
Institute of Bioorganic Chemistry of NAS of Belarus
Belarus
Belarus
Sachanka Antos B. – Researcher
5/2, Academician V. F. Kuprevich Str., 220084, Minsk
E. A. Popicheva
Institute of Bioorganic Chemistry of NAS of Belarus
Belarus
Belarus
Popicheva Ekaterina A. – Postgraduate Student
5/2, Academician V. F. Kuprevich Str., 220084, Minsk
V. V. Shchur
Institute of Bioorganic Chemistry of NAS of Belarus
Belarus
Belarus
Shchur Veronika V. – Ph. D. (Chemistry), Senior Researcher
5/2, Academician V. F. Kuprevich Str., 220084, Minsk
S. A. Usanov
Institute of Bioorganic Chemistry of NAS of Belarus
Belarus
Belarus
Usanov Sergei A. – Corresponding Member, Dr. Sci. (Chemistry), Professor, Chief Researcher
5/2, Academician V. F. Kuprevich Str., 220084, Minsk
A. V. Yantsevich
Institute of Bioorganic Chemistry of NAS of Belarus
Belarus
Belarus
Yantsevich Aliaksei V. – Ph. D. (Chemistry), Head of the Laboratory
5/2, Academician V. F. Kuprevich Str., 220084, Minsk
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