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Kho J, Pham PC, Kwon S, et al. De Novo Design, Synthesis, and Mechanistic Evaluation of Short Peptides That Mimic Heat Shock Protein 27 Activity. ACS Med Chem Lett. 2021;12(5):713-719doi: 10.1021/acsmedchemlett.0c00609.
Kho, J., Pham, P. C., Kwon, S., Huang, A. Y., Rivers, J. P., Wang, H., Ecroyd, H., Donald, W. A., & McAlpine, S. R. (2021). De Novo Design, Synthesis, and Mechanistic Evaluation of Short Peptides That Mimic Heat Shock Protein 27 Activity. ACS medicinal chemistry letters, 12(5), 713-719. https://doi.org/10.1021/acsmedchemlett.0c00609
Kho, Jessica, et al. "De Novo Design, Synthesis, and Mechanistic Evaluation of Short Peptides That Mimic Heat Shock Protein 27 Activity." ACS medicinal chemistry letters vol. 12,5 (2021): 713-719. doi: https://doi.org/10.1021/acsmedchemlett.0c00609
Kho J, Pham PC, Kwon S, Huang AY, Rivers JP, Wang H, Ecroyd H, Donald WA, McAlpine SR. De Novo Design, Synthesis, and Mechanistic Evaluation of Short Peptides That Mimic Heat Shock Protein 27 Activity. ACS Med Chem Lett. 2021 May 03;12(5):713-719. doi: 10.1021/acsmedchemlett.0c00609. eCollection 2021 May 13. PMID: 34055216; PMCID: PMC8155270.
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ACS Med Chem Lett. 2021 May 03;12(5):713-719. doi: 10.1021/acsmedchemlett.0c00609. eCollection 2021 May 13.

De Novo Design, Synthesis, and Mechanistic Evaluation of Short Peptides That Mimic Heat Shock Protein 27 Activity.

ACS medicinal chemistry letters

Jessica Kho, P Chi Pham, Suhyeon Kwon, Alana Y Huang, Joel P Rivers, Huixin Wang, Heath Ecroyd, W Alexander Donald, Shelli R McAlpine

Affiliations

  1. School of Chemistry, University of New South Wales, Sydney, NSW 2052, Australia.
  2. Department of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW 2522, Australia.
  3. School of Chemistry, University of California Irvine, Irvine, California 92697, United States.

PMID: 34055216 PMCID: PMC8155270 DOI: 10.1021/acsmedchemlett.0c00609

Abstract

We report the first small molecule peptides based on the N-terminal sequence of heat shock protein 27 (Hsp27, gene HSPB1) that demonstrates chaperone-like activity. The peptide, comprising the SWDPF sequence located at Hsp27's amino (N)-terminal domain, directly regulates protein aggregation events, maintaining the disaggregated state of the model protein, citrate synthase. While traditional inhibitors of protein aggregation act via regulation of a protein that facilitates aggregation or disaggregation, our molecules are the first small peptides between 5 and 8 amino acids in length that are based on the N-terminus of Hsp27 and directly control protein aggregation. The presented strategy showcases a new approach for developing small peptides that control protein aggregation in proteins with high aggregate levels, making them a useful approach in developing new drugs.

© 2021 American Chemical Society.

Conflict of interest statement

The authors declare no competing financial interest.

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