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

Journal Article


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.

Publication Date


  • 2021

Citation


  • Kho, J., Pham, P. C., Kwon, S., Huang, A. Y., Rivers, J. P., Wang, H., . . . 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. doi:10.1021/acsmedchemlett.0c00609

Scopus Eid


  • 2-s2.0-85106427260

Start Page


  • 713

End Page


  • 719

Volume


  • 12

Issue


  • 5

Place Of Publication


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.

Publication Date


  • 2021

Citation


  • Kho, J., Pham, P. C., Kwon, S., Huang, A. Y., Rivers, J. P., Wang, H., . . . 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. doi:10.1021/acsmedchemlett.0c00609

Scopus Eid


  • 2-s2.0-85106427260

Start Page


  • 713

End Page


  • 719

Volume


  • 12

Issue


  • 5

Place Of Publication