Scyllatoxin-based peptide design for E. coli expression and HIV gp120 binding.

Autor: Nurheibah SI; Department of Proteome Structural Biology, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, 34113, Republic of Korea; Disease Target Structure Research Center, KRIBB, Daejeon, 31441, Republic of Korea., Sayyed ND; Disease Target Structure Research Center, KRIBB, Daejeon, 31441, Republic of Korea; Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, 24341, Republic of Korea., Batyanovskii AV; United Institute of Informatics Problems, National Academy of Sciences of Belarus, Minsk, 220012, Belarus., Talwar CS; Department of Proteome Structural Biology, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, 34113, Republic of Korea; Disease Target Structure Research Center, KRIBB, Daejeon, 31441, Republic of Korea., Ahn WC; Critical Diseases Diagnostics Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea., Park KH; Department of Proteome Structural Biology, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, 34113, Republic of Korea; Critical Diseases Diagnostics Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea., Tuzikov AV; United Institute of Informatics Problems, National Academy of Sciences of Belarus, Minsk, 220012, Belarus., Ha KS; Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, 24341, Republic of Korea. Electronic address: ksha@kangwon.ac.kr., Woo EJ; Department of Proteome Structural Biology, KRIBB School of Bioscience, Korea University of Science and Technology (UST), Daejeon, 34113, Republic of Korea; Disease Target Structure Research Center, KRIBB, Daejeon, 31441, Republic of Korea. Electronic address: ejwoo@kribb.re.kr.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Oct 01; Vol. 727, pp. 150310. Date of Electronic Publication: 2024 Jun 25.
DOI: 10.1016/j.bbrc.2024.150310
Abstrakt: Targeting the hydrophobic Phe43 pocket of HIV's envelope glycoprotein gp120 is a critical strategy for antiviral interventions due to its role in interacting with the host cell's CD4. Previous inhibitors, including small molecules and CD4 mimetic peptides based on scyllatoxin, have demonstrated significant binding and neutralization capabilities but were often chemically synthesized or contained non-canonical amino acids. Microbial expression using natural amino acids offers advantages such as cost-effectiveness, scalability, and efficient production of fusion proteins. In this study, we enhanced the previous scyllatoxin-based synthetic peptide by substituting natural amino acids and successfully expressed it in E. coli. The peptide was optimized by mutating the C-terminal amidated valine to valine and glutamine, and by reducing the disulfide bonds from three to two. Circular dichroism confirmed proper secondary structure formation, and fluorescence polarization analysis revealed specific, concentration-dependent binding to HIV gp120, supported by molecular dynamics simulations. These findings indicate the potential for scalable microbial production of effective antiviral peptides, with significant applications in pharmaceutical development for HIV treatment.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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