The Construction of a Genetically Encoded, Phage-Displayed Cyclic-Peptide Library
© 2021. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature..
Due to the great potentials of cyclic peptides as therapeutic agents, several phage-displayed peptide libraries in which cyclization is achieved by the covalent linkage of cysteines have been previously demonstrated to identify cyclic-peptide ligands for therapeutic targets. While problems remain in these cysteine conjugation strategies, we have invented a phage display technique in which its displayed peptides are cyclized through a proximity-driven Michael addition reaction between a cysteine and an amber-codon-encoded Nε-acryloyl-lysine (AcrK). Using a randomized 6-mer library in which peptides were cyclized at two ends through a cysteine-AcrK linker, we demonstrated the successful selection of a potent ligand, CycH8a, for histone deacetylase 8 (HDAC8). We believe this approach will find broad applications in drug discovery.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:2355 |
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| Enthalten in: |
Methods in molecular biology (Clifton, N.J.) - 2355(2021) vom: 12., Seite 219-230 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chen, Peng-Hsun Chase [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 11.01.2022 Date Revised 11.01.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1007/978-1-0716-1617-8_17 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM329307436 |
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| 520 | |a Due to the great potentials of cyclic peptides as therapeutic agents, several phage-displayed peptide libraries in which cyclization is achieved by the covalent linkage of cysteines have been previously demonstrated to identify cyclic-peptide ligands for therapeutic targets. While problems remain in these cysteine conjugation strategies, we have invented a phage display technique in which its displayed peptides are cyclized through a proximity-driven Michael addition reaction between a cysteine and an amber-codon-encoded Nε-acryloyl-lysine (AcrK). Using a randomized 6-mer library in which peptides were cyclized at two ends through a cysteine-AcrK linker, we demonstrated the successful selection of a potent ligand, CycH8a, for histone deacetylase 8 (HDAC8). We believe this approach will find broad applications in drug discovery | ||
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