vestichИзвестия Национальной академии наук Беларуси. Серия химических наукProceedings of the National Academy of Sciences of Belarus, Chemical Series1561-83312524-2342The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1561-8331-2026-62-1-57-70vestich-1001Research ArticleБИООРГАНИЧЕСКАЯ ХИМИЯBIOORGANIC CHEMISTRYКонструирование комплексного стимулятора ангиогенеза на основе гибридного белка ANGPT1_VEGF165Construction of a complex stimulator of angiogenesis based on the fusion protein ANGPT1_VEGF165СаченкоА. Б.SachankaA. B.

Саченко Антон Борисович – научный сотрудник 

ул. Академика В. Ф. Купревича, 5/2, 220084, Минск

Sachanka Antos B. – Researcher

5/2, Academician V. F. Kuprevich Str., 220084, Minsk

antosuk@yandex.ruПопичеваЕ. А.PopichevaE. A.

Попичева Екатерина Александровна – аспирант 

ул. Академика В. Ф. Купревича, 5/2, 220084, Минск

Popicheva Ekaterina A. – Postgraduate Student 

5/2, Academician V. F. Kuprevich Str., 220084, Minsk

ekaterinapopicheva@mail.ruЩурВ. B.ShchurV. V.

Щур Вероника Владимировна – кандидат химических наук, старший научный сотрудник 

ул. Академика В. Ф. Купревича, 5/2, 220084, Минск

Shchur Veronika V. – Ph. D. (Chemistry), Senior Researcher 

5/2, Academician V. F. Kuprevich Str., 220084, Minsk

shchur931@gmail.comУсановС. А.UsanovS. A.

Усанов Сергей Александрович – член-корреспондент, доктор химических наук, професор, главный научный сотрудник 

ул. Академика В. Ф. Купревича, 5/2, 220084, Минск

Usanov Sergei A. – Corresponding Member, Dr. Sci. (Chemistry), Professor, Chief Researcher 

5/2, Academician V. F. Kuprevich Str., 220084, Minsk

usanov@iboch.byЯнцевичА. В.YantsevichA. V.

Янцевич Алексей Викторович – кандидат химических наук, заведующий лабораторией 

ул. Академика В. Ф. Купревича, 5/2, 220084, Минск

Yantsevich Aliaksei V.  –  Ph.  D.  (Chemistry),  Head of the Laboratory 

5/2, Academician V. F. Kuprevich Str., 220084, Minsk

al.yantsevich@gmail.comИнститут биоорганической химии Национальной академии наук БеларусиInstitute of Bioorganic Chemistry of NAS of Belarus2026040320266215770Copyright © Саченко А.Б., Попичева Е.А., Щур В.B., Усанов С.А., Янцевич А.В., 20262026Саченко А.Б., Попичева Е.А., Щур В.B., Усанов С.А., Янцевич А.В.Sachanka A.B., Popicheva E.A., Shchur V.V., Usanov S.A., Yantsevich A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestichem.belnauka.by/jour/article/view/1001

Белки VEGF165 и ANGPT1 являются ключевыми регуляторами ангиогенеза, что лежит в основе терапевтических подходов к лечению хронической ишемии нижних конечностей. Конструирование гибридного белка на их основе потенциально способно значительно усилить терапевтический эффект. Для определения оптимального расположения функциональных доменов гибридного белка (VEGF165_ANGPT1 или ANGPT1_VEGF165), а также для установления оптимальной длины и аминокислотного состава пептидного линкера между двумя белками проведен анализ траекторий молекулярной динамики и пространственных структур 134 гибридных белков. Определены оптимальные линкеры для ANGPT1_VEGF165: GGGSGGGGSGGGSGGGS, GGGGSGGGGSGGGGS, GGGSGGGGS, PAPAPAP и для VEGF165_ANGPT1: GGGGSGGGGGS, GGGSGGGGSGGGGSGGGS, GGGGSGGGGSGGGGSGGGGS, которые способствуют повышению стабильности гибридных белков. По результатам исследования отобран вариант ANGPT1_VEGF165 с линкером GGGSGGGGSGGGSGGGS для анализа его функциональной активности.

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.

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The authors declare that there are no conflicts of interest present.