Design and synthesis of peptide-based chimeric molecules to induce degradation of the estrogen and androgen receptors
[Display omitted] Peptide-based inducers of estrogen receptor (ER) α and androgen receptor (AR) degradations via the ubiquitin–proteasome system (UPS) were developed. The designated inducers were composed of two biologically active scaffolds: the helical peptide PERM3, which is an LXXLL-like mimic o...
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| Published in | Bioorganic & medicinal chemistry Vol. 28; no. 15; pp. 115595 - 115599 |
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| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
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01.08.2020
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| Abstract | [Display omitted]
Peptide-based inducers of estrogen receptor (ER) α and androgen receptor (AR) degradations via the ubiquitin–proteasome system (UPS) were developed. The designated inducers were composed of two biologically active scaffolds: the helical peptide PERM3, which is an LXXLL-like mimic of the coactivator SRC-1, and various small molecules (MV1, LCL161, VH032, and POM) that bind to E3 ligases (IAPs, VHL, and cereblon, respectively), to induce ubiquitylation of nuclear receptors that bind to SRC-1. All of the synthesized chimeric E3 ligand-containing molecules induced the UPS-mediated degradation of ERα and AR. The PERM3 peptide was applicable for the development of the ERα and AR degraders using these E3 ligands. |
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| AbstractList | Peptide-based inducers of estrogen receptor (ER) alpha and androgen receptor (AR) degradations via the ubiquitin-proteasome system (UPS) were developed. The designated inducers were composed of two biologically active scaffolds: the helical peptide PERM3, which is an LXXLL-like mimic of the coactivator SRC-1, and various small molecules (MV1, LCL161, VH032, and POM) that bind to E3 ligases (IAPs, VHL, and cereblon, respectively), to induce ubiquitylation of nuclear receptors that bind to SRC-1. All of the synthesized chimeric E3 ligand-containing molecules induced the UPS-mediated degradation of ER alpha and AR. The PERM3 peptide was applicable for the development of the ER alpha and AR degraders using these E3 ligands. Peptide-based inducers of estrogen receptor (ER) α and androgen receptor (AR) degradations via the ubiquitin-proteasome system (UPS) were developed. The designated inducers were composed of two biologically active scaffolds: the helical peptide PERM3, which is an LXXLL-like mimic of the coactivator SRC-1, and various small molecules (MV1, LCL161, VH032, and POM) that bind to E3 ligases (IAPs, VHL, and cereblon, respectively), to induce ubiquitylation of nuclear receptors that bind to SRC-1. All of the synthesized chimeric E3 ligand-containing molecules induced the UPS-mediated degradation of ERα and AR. The PERM3 peptide was applicable for the development of the ERα and AR degraders using these E3 ligands.Peptide-based inducers of estrogen receptor (ER) α and androgen receptor (AR) degradations via the ubiquitin-proteasome system (UPS) were developed. The designated inducers were composed of two biologically active scaffolds: the helical peptide PERM3, which is an LXXLL-like mimic of the coactivator SRC-1, and various small molecules (MV1, LCL161, VH032, and POM) that bind to E3 ligases (IAPs, VHL, and cereblon, respectively), to induce ubiquitylation of nuclear receptors that bind to SRC-1. All of the synthesized chimeric E3 ligand-containing molecules induced the UPS-mediated degradation of ERα and AR. The PERM3 peptide was applicable for the development of the ERα and AR degraders using these E3 ligands. [Display omitted] Peptide-based inducers of estrogen receptor (ER) α and androgen receptor (AR) degradations via the ubiquitin–proteasome system (UPS) were developed. The designated inducers were composed of two biologically active scaffolds: the helical peptide PERM3, which is an LXXLL-like mimic of the coactivator SRC-1, and various small molecules (MV1, LCL161, VH032, and POM) that bind to E3 ligases (IAPs, VHL, and cereblon, respectively), to induce ubiquitylation of nuclear receptors that bind to SRC-1. All of the synthesized chimeric E3 ligand-containing molecules induced the UPS-mediated degradation of ERα and AR. The PERM3 peptide was applicable for the development of the ERα and AR degraders using these E3 ligands. Peptide-based inducers of estrogen receptor (ER) α and androgen receptor (AR) degradations via the ubiquitin-proteasome system (UPS) were developed. The designated inducers were composed of two biologically active scaffolds: the helical peptide PERM3, which is an LXXLL-like mimic of the coactivator SRC-1, and various small molecules (MV1, LCL161, VH032, and POM) that bind to E3 ligases (IAPs, VHL, and cereblon, respectively), to induce ubiquitylation of nuclear receptors that bind to SRC-1. All of the synthesized chimeric E3 ligand-containing molecules induced the UPS-mediated degradation of ERα and AR. The PERM3 peptide was applicable for the development of the ERα and AR degraders using these E3 ligands. |
| ArticleNumber | 115595 |
| Author | Yokoo, Hidetomo Demizu, Yosuke Naito, Mikihiko Ohoka, Nobumichi |
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| Keywords | Protein knockdown Helical peptide Nuclear receptors Protein–protein interaction Protein-protein interaction PROTEIN-DEGRADATION UBIQUITIN LIGASE HELICAL PEPTIDES INHIBITORS |
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Peptide-based inducers of estrogen receptor (ER) α and androgen receptor (AR) degradations via the ubiquitin–proteasome system (UPS) were... Peptide-based inducers of estrogen receptor (ER) alpha and androgen receptor (AR) degradations via the ubiquitin-proteasome system (UPS) were developed. The... Peptide-based inducers of estrogen receptor (ER) α and androgen receptor (AR) degradations via the ubiquitin-proteasome system (UPS) were developed. The... |
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| Title | Design and synthesis of peptide-based chimeric molecules to induce degradation of the estrogen and androgen receptors |
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