Development of stapled NONO-associated peptides reveals unexpected cell permeability and nuclear localisation
© 2023 The Authors. Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd..
The non-POU domain-containing octamer-binding protein (NONO) is a nucleic acid-binding protein with diverse functions that has been identified as a potential cancer target in cell biology studies. Little is known about structural motifs that mediate binding to NONO apart from its ability to form homodimers, as well as heterodimers and oligomers with related homologues. We report a stapling approach to macrocyclise helical peptides derived from the insulin-like growth factor binding protein (IGFBP-3) that NONO interacts with, and also from the dimerisation domain of NONO itself. Using a range of chemistries including Pd-catalysed cross-coupling, cysteine arylation and cysteine alkylation, we successfully improved the helicity and observed modest peptide binding to the NONO dimer, although binding could not be saturated at micromolar concentrations. Unexpectedly, we observed cell permeability and preferential nuclear localisation of various dye-labelled peptides in live confocal microscopy, indicating the potential for developing peptide-based tools to study NONO in a cellular context.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
Journal of peptide science : an official publication of the European Peptide Society - 30(2024), 5 vom: 06. Apr., Seite e3562 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Young, Reginald [VerfasserIn] |
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| Links: |
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| Themen: |
Alpha helix |
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| Anmerkungen: |
Date Completed 08.04.2024 Date Revised 08.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/psc.3562 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a © 2023 The Authors. Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd. | ||
| 520 | |a The non-POU domain-containing octamer-binding protein (NONO) is a nucleic acid-binding protein with diverse functions that has been identified as a potential cancer target in cell biology studies. Little is known about structural motifs that mediate binding to NONO apart from its ability to form homodimers, as well as heterodimers and oligomers with related homologues. We report a stapling approach to macrocyclise helical peptides derived from the insulin-like growth factor binding protein (IGFBP-3) that NONO interacts with, and also from the dimerisation domain of NONO itself. Using a range of chemistries including Pd-catalysed cross-coupling, cysteine arylation and cysteine alkylation, we successfully improved the helicity and observed modest peptide binding to the NONO dimer, although binding could not be saturated at micromolar concentrations. Unexpectedly, we observed cell permeability and preferential nuclear localisation of various dye-labelled peptides in live confocal microscopy, indicating the potential for developing peptide-based tools to study NONO in a cellular context | ||
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| 700 | 1 | |a Luo, Zijie |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Yaw Sing |e verfasserin |4 aut | |
| 700 | 1 | |a Kaur, Amandeep |e verfasserin |4 aut | |
| 700 | 1 | |a Lau, Yu Heng |e verfasserin |4 aut | |
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