79-83-4Relevant academic research and scientific papers
Chemical Proteomic Profiling of Protein 4′-Phosphopantetheinylation in Mammalian Cells
Chen, Nan,Li, Yuanpei,Liu, Yuan,Wang, Chu
supporting information, p. 16069 - 16075 (2020/07/21)
Protein 4′-phosphopantetheinylation is an essential post-translational modification (PTM) in prokaryotes and eukaryotes. So far, only five protein substrates of this specific PTM have been discovered in mammalian cells. These proteins are known to perform important functions, including fatty acid biosynthesis and folate metabolism, as well as β-alanine activation. To explore existing and new substrates of 4′-phosphopantetheinylation in mammalian proteomes, we designed and synthesized a series of new pantetheine analogue probes, enabling effective metabolic labelling of 4′-phosphopantetheinylated proteins in HepG2 cells. In combination with a quantitative chemical proteomic platform, we enriched and identified all the currently known 4′-phosphopantetheinylated proteins with high confidence, and unambiguously determined their exact sites of modification. More encouragingly, we discovered, using targeted chemical proteomics, a potential 4′-phosphopantetheinylation site in the protein of mitochondrial dehydrogenase/reductase SDR family member 2 (DHRS2).
PANTETHENOYLCYSTEINE DERIVATIVES AND USES THEREOF
-
Paragraph 3255-3256, (2020/10/20)
The present disclosure relates to compounds of Formula (I) or (II): (Formulae (I), (II)), and pharmaceutically acceptable salts or solvates thereof. The present disclosure also relates to pharmaceutical compositions comprising the compounds and therapeutic and diagnostic uses of the compounds and pharmaceutical compositions.
PANTETHEINE DERIVATIVES AND USES THEREOF
-
Paragraph 2065, (2020/06/19)
The present disclosure relates to compounds of Formula (I), (II), or (II'): (I), (II), (II'), and pharmaceutically acceptable salts or solvates thereof. The present disclosure also relates to pharmaceutical compositions comprising the compounds and therapeutic and diagnostic uses of the compounds and pharmaceutical compositions.
Modular Enzymatic Cascade Synthesis of Vitamin B5 and Its Derivatives
Abidin, Mohammad Z.,Saravanan, Thangavelu,Zhang, Jielin,Tepper, Pieter G.,Strauss, Erick,Poelarends, Gerrit J.
supporting information, p. 17434 - 17438 (2018/11/10)
Access to vitamin B5 [(R)-pantothenic acid] and both diastereoisomers of α-methyl-substituted vitamin B5 [(R)- and (S)-3-((R)-2,4-dihydroxy-3,3-dimethylbutanamido)-2-methylpropanoic acid] was achieved using a modular three-step biocatalytic cascade involving 3-methylaspartate ammonia lyase (MAL), aspartate-α-decarboxylase (ADC), β-methylaspartate-α-decarboxylase (CrpG) or glutamate decarboxylase (GAD), and pantothenate synthetase (PS) enzymes. Starting from simple non-chiral dicarboxylic acids (either fumaric acid or mesaconic acid), vitamin B5 and both diastereoisomers of α-methyl-substituted vitamin B5, which are valuable precursors for promising antimicrobials against Plasmodium falciparum and multidrug-resistant Staphylococcus aureus, can be generated in good yields (up to 70 %) and excellent enantiopurity (>99 % ee). This newly developed cascade process may be tailored and used for the biocatalytic production of various vitamin B5 derivatives by modifying the pantoyl or β-alanine moiety.
Probing the ligand preferences of the three types of bacterial pantothenate kinase
Guan, Jinming,Barnard, Leanne,Cresson, Jeanne,Hoegl, Annabelle,Chang, Justin H.,Strauss, Erick,Auclair, Karine
supporting information, p. 5896 - 5902 (2018/11/23)
Pantothenate kinase (PanK) catalyzes the transformation of pantothenate to 4′-phosphopantothenate, the first committed step in coenzyme A biosynthesis. While numerous pantothenate antimetabolites and PanK inhibitors have been reported for bacterial type I and type II PanKs, only a few weak inhibitors are known for bacterial type III PanK enzymes. Here, a series of pantothenate analogues were synthesized using convenient synthetic methodology. The compounds were exploited as small organic probes to compare the ligand preferences of the three different types of bacterial PanK. Overall, several new inhibitors and substrates were identified for each type of PanK.
Ratiometric Fluorescent Probe for Imaging of Pantetheinase in Living Cells
Hu, Yiming,Li, Hongyu,Shi, Wen,Ma, Huimin
, p. 11107 - 11112 (2017/10/20)
Pantetheinase, which catalyzes the cleavage of pantetheine to pantothenic acid (vitamin B5) and cysteamine, is involved in the regulation of oxidative stress, pantothenate recycling and cell migration. However, further elucidating the cellular function of this enzyme is largely limited by the lack of a suitable fluorescence imaging probe. By conjugating pantothenic acid with cresyl violet, herein we develop a new fluorescence probe CV-PA for the assay of pantetheinase. The probe not only possesses long analytical wavelengths but also displays linear ratiometric (I628/582 nm) fluorescence response to pantetheinase in the range of 5-400 ng/mL with a detection limit of 4.7 ng/mL. This probe has been used to evaluate the efficiency of different inhibitors and quantitatively detect pantetheinase in serum samples, revealing that pantetheinase in fetal bovine serum and new born calf serum is much higher than that in normal human serum. Notably, with the probe the ratiometric imaging and in situ quantitative comparison of pantetheinase in different living cells (LO2 and HK-2) have been achieved for the first time. It is found that the level of pantetheinase in LO2 cells is much larger than that in HK-2 cells, as further validated by Western blot analysis. The proposed probe may be useful to better understand the specific function of pantetheinase in the pantetheinase-related pathophysiological processes. (Graph Presented).
Enantiodivergent syntheses of pantolactone and pantothenic acid from d -mannitol
Sanyal, Ishita,Barman, Piyalideb,Banerjee, Asishkumar
, p. 1102 - 1108 (2012/05/04)
Efficient synthetic routes to both the enantiomers of pantolactone and pantothenic acid have been developed starting from d-mannitol-based d-glyceraldehyde acetonide through its conversion into a protected pantoic acid intermediate followed by either cyclization or amide bond formation with a -amino ester, and subsequent appropriate deprotection. Georg Thieme Verlag Stuttgart . New York.
Fast and flexible synthesis of pantothenic acid and CJ-15,801
Sewell, Alan L.,Villa, Mathew V. J.,Matheson, Mhairi,Whittingham, William G.,Marquez, Rodolfo
, p. 800 - 803 (2011/04/25)
The fast and efficient syntheses of pantothenic acid and the antiparasitic agent CJ-15,801 have been achieved starting from a common imide unit through the selective manipulation of enamide intermediates.
A fluorescent assay suitable for inhibitor screening and vanin tissue quantification
Ruan, Benfang H.,Cole, Derek C.,Wu, Paul,Quazi, Amira,Page, Karen,Wright, Jill F.,Huang, Nelson,Stock, Joseph R.,Nocka, Karl,Aulabaugh, Ann,Krykbaev, Rustem,Fitz, Lori J.,Wolfman, Neil M.,Fleming, Margaret L.
experimental part, p. 284 - 292 (2011/12/03)
Vanin-1 is a pantetheinase that catalyzes the hydrolysis of pantetheine to produce pantothenic acid (vitamin B5) and cysteamine. Reported here is a highly sensitive fluorescent assay using a novel fluorescently labeled pantothenate derivative. The assay has been used for characterization of a soluble version of human vanin-1 recombinant protein, identification and characterization of hits from high-throughput screening (HTS), and quantification of vanin pantothenase activity in cell lines and tissues. Under optimized assay conditions, we quantified vanin pantothenase activity in tissue lysate and found low activity in lung and liver but high activity in kidney. We demonstrated that the purified recombinant vanin-1 consisting of the extracellular portion without the glycosylphosphatidylinositol (GPI) linker was highly active with an apparent Km of 28 μM for pantothenate-7-amino-4-methylcoumarin (pantothenate-AMC), which was converted to pantothenic acid and AMC based on liquid chromatography-mass spectrometry (LC-MS) analysis. The assay also performed well in a 384-well microplate format under initial rate conditions (10% conversion) with a signal-to-background ratio (S/B) of 7 and a Z factor of 0.75. Preliminary screening of a library of 1280 pharmaceutically active compounds identified inhibitors with novel chemical scaffolds. This assay will be a powerful tool for target validation and drug lead identification and characterization.
A highly convergent synthesis of myristoyl-carba(dethia)-coenzyme A
Tautz, Lutz,Retey, Janos
experimental part, p. 1728 - 1735 (2010/06/13)
Co-translational myristoylation of the N-terminal glycine residues of diverse signalling proteins is required for membrane attachment and proper function of these molecules. The transfer of myristate from myristoyl-coenzyme A (myr-CoA) is catalysed by the enzyme N-myristoyltransferase (Nmt). Nmt has been implicated in a number of human diseases, including cancer and epilepsy, as well as in pathogenic mechanisms such as fungal and virus infections, including HIV and hepatitis B. Rational design has led to the development of potent competitive inhibitors, including several nonhydrolysable acyl-CoA substrate analogues. Linear synthetic strategies, following the route of the original CoA synthesis, however, generate such analogues in very low overall yields that typically are not sufficient for in vivo studies. Here we present a new, highly convergent synthesis of myristoylcarba(dethia)-coenzyme A (1) that allows this substrate analogue to be obtained in a yield 11 times higher than that of the reported linear synthesis. In addition, enzymatic cleavage of the adenosine-2′,3′-cyclophosphate in the last step of the synthesis proved to be an efficient way to obtain the isomerically pure 3′-phosphate 1 free of the 2′-phosphate 13.
