Synthesis of SARS-CoV-2 Spike Glycoprotein Peptide Fragments and Study of Their Binding to Human Blood Cells

IF 1.1 4区 化学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Russian Journal of Bioorganic Chemistry Pub Date : 2024-10-09 DOI:10.1134/S1068162024050352
О. V. Gribovskaya, V. V. Yanchenko, A. M. Tsygankov, V. P. Martinovich
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Abstract

Objective: Тhe development of new proteins against COVID-19 is an urgent task. The goal of this work was the synthesis of the peptides Lys-Ile-Ala-Asp-Tyr-Asn-Tyr-Lys-Leu (417–425 aa) and Val-Arg-Gln-Ala-Pro-Asn-Gly- Gln-Thr (407–415 aa) – fragments of the surface glycoprotein Spike of SARS-CoV-2 – as potential components of a vaccine against COVID-19 and the study of their binding to human blood cells. Methods: The compounds were synthesized using peptide chemistry methods in solution. The effect of peptides on leukocytes was studied by flow cytometry using monoclonal antibodies against molecules expressed on leukocytes (CD45), that are responsible for the early activation of lymphocytes (CD69) and basophils (CD203c, CD63). The concentration of IFN-γ, which was secreted by lymphocytes in response to peptides, was determined by ELISA. Results and Discussion: It was established that peptides could bind to leukocytes, which indicates the universality of reactions to peptides, especially in innate immune cells. It was shown that the Lys-Ile-Ala-Asp-Tyr-Asn-Tyr-Lys-Leu peptide contacted the leukocytes activated the lymphocytes and basophils. It was confirmed by an increase in gamma interferon compared to the Val-Arg-Gln-Ala-Pro-Asn-Gly-Gln-Thr. Conclusions: A method that allows to evaluate the effect of short peptides on leukocytes was tested. It was shown that the obtained peptides interact with leukocytes, activating them, which was evidenced by secretion of IFN-γ. Our proposed method for evaluating the effect of short peptides on blood cells is the first step in the development of a new peptide-based vaccine against COVID-19.

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SARS-CoV-2 穗状糖蛋白肽片段的合成及其与人类血细胞结合的研究
目标开发针对 COVID-19 的新蛋白质是一项紧迫任务。这项工作的目标是合成 SARS-CoV-2 表面糖蛋白 Spike 的多肽 Lys-Ile-Ala-Asp-Tyr-Asn-Tyr-Lys-Leu (417-425 aa) 和 Val-Arg-Gln-Ala-Pro-Asn-Gly-Gln-Thr (407-415 aa),作为 COVID-19 疫苗的潜在成分,并研究它们与人血细胞的结合情况。研究方法这些化合物是用多肽化学方法在溶液中合成的。使用针对白细胞上表达的分子(CD45)、淋巴细胞早期活化分子(CD69)和嗜碱性粒细胞分子(CD203c、CD63)的单克隆抗体,通过流式细胞术研究肽对白细胞的影响。用酶联免疫吸附法测定了淋巴细胞对多肽反应分泌的 IFN-γ 的浓度。结果与讨论:研究证实肽能与白细胞结合,这表明肽反应的普遍性,尤其是先天性免疫细胞。研究表明,Lys-Ile-Ala-Asp-Tyr-Asn-Tyr-Lys-Leu 多肽与白细胞接触后可激活淋巴细胞和嗜碱性粒细胞。与 Val-Arg-Gln-Ala-Pro-Asn-Gly-Gln-Thr 相比,γ 干扰素的增加证实了这一点。结论我们测试了一种评估短肽对白细胞影响的方法。结果表明,获得的短肽能与白细胞相互作用,激活白细胞,并通过分泌 IFN-γ 证明了这一点。我们提出的评估短肽对血细胞影响的方法是开发基于短肽的新型 COVID-19 疫苗的第一步。
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来源期刊
Russian Journal of Bioorganic Chemistry
Russian Journal of Bioorganic Chemistry 生物-生化与分子生物学
CiteScore
1.80
自引率
10.00%
发文量
118
审稿时长
3 months
期刊介绍: Russian Journal of Bioorganic Chemistry publishes reviews and original experimental and theoretical studies on the structure, function, structure–activity relationships, and synthesis of biopolymers, such as proteins, nucleic acids, polysaccharides, mixed biopolymers, and their complexes, and low-molecular-weight biologically active compounds (peptides, sugars, lipids, antibiotics, etc.). The journal also covers selected aspects of neuro- and immunochemistry, biotechnology, and ecology.
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