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...

Full description

Saved in:
Bibliographic Details
Published inBiomolecules (Basel, Switzerland) Vol. 12; no. 8; p. 1065
Main Authors Löcherer, Christian, Tosun, Elif, Backes, Hannah, Jäschke, Andres
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 01.08.2022
MDPI
Subjects
Adenosine triphosphate
Analysis
Biomimetics
Biotransformation
Chromatography
CoA
CoA biosynthesis
CoA degradation
Coenzyme A
Coenzymes
Communication
Decomposition (Chemistry)
E coli
Enzymes
Health aspects
Hydrolysis
Identification and classification
Intracellular
Kinases
Mass spectrometry
Methods
Neurodegeneration
NMR
Nuclear magnetic resonance
Nudt7
Observations
phosphorothioate
Phosphorylation
Plasmids
PPanSH
Proteins
Scientific imaging
Signal transduction
Thiophosphate
Germany
United Kingdom > UK
Online AccessGet full text

Cover

More Information
Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:2218-273X
2218-273X
DOI:10.3390/biom12081065