Abstract
New drugs and vaccines are urgently needed for malaria control owing to the increasing prevalence of drug-resistant Plasmodium strains. Malarial merozoite surface protein 2 (MSP2), potentially playing a role in parasite invasion into the host red blood cells, could be a target for anti-malaria drug development. MSP2 is suggested to cause membrane disruption that is correlated with amyloidogenesis of the protein, and thus peptides that can inhibit this property may be exploited as drug candidates against malaria. In this study, we designed peptides by introducing residues that favor β-turn formation into the amyloidogenic N-terminal segment between the 8th and 22nd residues of MSP2 (MSP28–22), and evaluated the ability of these derivative peptides to inhibit MSP2 amyloidogenesis and membrane disruption. One of the derivative peptides, M5, with a β-turn-prone sequence DPDG being inserted within MSP28–22, though did not form a rigid β-turn structure, did inhibit aggregation and membrane interaction by both itself and the wild-type peptide. Insertion of a β-turn-prone sequence may thus be a potential strategy to develop safe and effective peptide inhibitors against amyloidogeneic protein/peptide.
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Data Availability
The datasets generated during this study are included in this published article or available from the corresponding author on reasonable request.
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Acknowledgements
We thank Professor Raymond S. Norton and Doctor Christopher A. MacRaild of Monash University and Professor Robin F. Anders of La Trobe University for helpful discussion, and thank Doctor Hongxin Zhao and Professor Junfeng Wang of Chinese Academy of Sciences for kindly gifting SUVs.
Funding
This work was supported by the National Natural Science Foundation of China (Grant Number 31470775) and the Australia China Young Scientists Exchange Program (Grant Number 2015).
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ZX and ZX conceived the work and designed the experiments, ZX, ZJ, LC, and ZY performed the experiments and analyzed the data, ZX and ZX interpreted the data and drafted the manuscript. All authors read and approved the final manuscript.
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Zheng, X., Zhang, J., Lu, C. et al. Rational Design of Peptide Inhibitor Against Amyloidogenesis-Correlated Membrane Disruption by Merozoite Surface Protein 2. Int J Pept Res Ther 27, 1657–1666 (2021). https://doi.org/10.1007/s10989-021-10198-9
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DOI: https://doi.org/10.1007/s10989-021-10198-9