Rational design of peptide inhibitors targeting HSP90-CDC37 protein-protein interaction
Background: Specifically blocking HSP90-CDC37 interaction is emerging as a prospective strategy for cancer therapy. Aim: Applying a kinase pseudopeptide rationale to the discovery of HSP90-CDC37 protein-protein interaction (PPI) inhibitors. Methods: Pseudosubstrates were identified through sequence alignment and evaluated by biolayer interferometry assay, co-immunoprecipitation assay and antiproliferation assay. Results: TAT-DDO-59120 was identified to disrupt HSP90-CDC37 PPI through directly binding to HSP90, both extracellularly and intracellularly. In addition, the identified peptide showed ideal antiproliferative activity against the colorectal cancer cell HCT116 (IC50 = 12.82 μM). Conclusion: Compared with the traditional method of screening a large compound library to identify PPI inhibitors, this method is rapid and efficient with strong purpose, which provides a novel strategy for designing HSP90-CDC37 PPI inhibitors.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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| Enthalten in: |
Future medicinal chemistry - 16(2024), 2 vom: 31. Jan., Seite 125-138 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Qiuyue [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 19.01.2024 Date Revised 19.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4155/fmc-2023-0320 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366797905 |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Background: Specifically blocking HSP90-CDC37 interaction is emerging as a prospective strategy for cancer therapy. Aim: Applying a kinase pseudopeptide rationale to the discovery of HSP90-CDC37 protein-protein interaction (PPI) inhibitors. Methods: Pseudosubstrates were identified through sequence alignment and evaluated by biolayer interferometry assay, co-immunoprecipitation assay and antiproliferation assay. Results: TAT-DDO-59120 was identified to disrupt HSP90-CDC37 PPI through directly binding to HSP90, both extracellularly and intracellularly. In addition, the identified peptide showed ideal antiproliferative activity against the colorectal cancer cell HCT116 (IC50 = 12.82 μM). Conclusion: Compared with the traditional method of screening a large compound library to identify PPI inhibitors, this method is rapid and efficient with strong purpose, which provides a novel strategy for designing HSP90-CDC37 PPI inhibitors | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a HSP90–CDC37 PPI inhibitor | |
| 650 | 4 | |a pseudosubstrate | |
| 650 | 4 | |a rational design | |
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| 700 | 1 | |a Yan, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yuxuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Lixiao |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Jia |e verfasserin |4 aut | |
| 700 | 1 | |a You, Qidong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Lei |e verfasserin |4 aut | |
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