Thiophosphate analogs of coenzyme A and its precursors: synthesis, stability, and biomimetic potential
Coenzyme A (CoA) is ubiquitous and essential for key cellular processes in any living organism. Primary degradation of CoA occurs by enzyme-mediated pyrophosphate hydrolysis intracellularly and extracellularly to form adenosine 3’,5’-diphosphate and 4’-phosphopantetheine (PPanSH). The latter can be...
Gespeichert in:
| Hauptverfasser: | , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
1 August 2022
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| In: |
Biomolecules
Year: 2022, Jahrgang: 12, Heft: 8, Pages: 1-9 |
| ISSN: | 2218-273X |
| DOI: | 10.3390/biom12081065 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/biom12081065 Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2218-273X/12/8/1065 
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| Verfasserangaben: | Christian Löcherer, Elif Tosun, Hannah Backes and Andres Jäschke |
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| 520 | |a Coenzyme A (CoA) is ubiquitous and essential for key cellular processes in any living organism. Primary degradation of CoA occurs by enzyme-mediated pyrophosphate hydrolysis intracellularly and extracellularly to form adenosine 3’,5’-diphosphate and 4’-phosphopantetheine (PPanSH). The latter can be recycled for intracellular synthesis of CoA. Impairments in the CoA biosynthetic pathway are linked to a severe form of neurodegeneration with brain iron accumulation for which no disease-modifying therapy is available. Currently, exogenous administration of PPanSH is examined as a therapeutic intervention. Here, we describe biosynthetic access to thiophosphate analogs of PPanSH, 3′-dephospho-CoA, and CoA. The stabilizing effect of thiophosphate modifications toward degradation by extracellular and peroxisomal enzymes was studied in vitro. Experiments in a CoA-deficient cell model suggest a biomimetic potential of the PPanSH thiophosphate analog PSPanSH (C1). According to our findings, the administration of PSPanSH may provide an alternative approach to support intracellular CoA-dependent pathways. | ||
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| 650 | 4 | |a CoA deficiency | |
| 650 | 4 | |a CoA degradation | |
| 650 | 4 | |a HoPan | |
| 650 | 4 | |a NBIA | |
| 650 | 4 | |a Nudt7 | |
| 650 | 4 | |a phosphorothioate | |
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