A Definitive Synthesis of<scp>D</scp>‐<i>myo</i>‐Inositol 1,4,5,6‐Tetrakisphosphate and Its Enantiomer<scp>D</scp>‐<i>myo</i>‐Inositol 3,4,5,6‐Tetrakisphosphate from a Novel Butane‐2,3‐diacetal‐Protected Inositol

Mills, Stephen; Riley, Andrew M.; Liu, Changsheng; Mahon, Mary F.; Potter, Barry V. L.

doi:10.1002/chem.200305207

Cited by 12 publications

(2 citation statements)

References 39 publications

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“…Ins(1,3,4,5,6)P 5 used as substrate for IPK1 was synthesized according to published procedures [22] and did not show evidence of phosphate migration. InsP 4 s and InsP 3 s were obtained from Cayman Chemical Company or were synthesized according to published procedures [23]. Comparisons made between different enantiomers of enantiomeric pairs were performed with compounds obtained from one source only.…”

Section: Inositol Phosphatesmentioning

confidence: 99%

An ATP-responsive metabolic cassette comprised of inositol tris/tetrakisphosphate kinase 1 (ITPK1) and inositol pentakisphosphate 2-kinase (IPK1) buffers diphosphosphoinositol phosphate levels

Whitfield

White

Sprigg

et al. 2020

Biochemical Journal

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Inositol polyphosphates are ubiquitous molecular signals in metazoans, as are their pyrophosphorylated derivatives that bear a so-called ‘high-energy’ phosphoanhydride bond. A structural rationale is provided for the ability of Arabidopsis inositol tris/tetrakisphosphate kinase 1 to discriminate between symmetric and enantiomeric substrates in the production of diverse symmetric and asymmetric myo-inositol phosphate and diphospho-myo-inositol phosphate (inositol pyrophosphate) products. Simple tools are applied to chromatographic resolution and detection of known and novel diphosphoinositol phosphates without resort to radiolabeling approaches. It is shown that inositol tris/tetrakisphosphate kinase 1 and inositol pentakisphosphate 2-kinase comprise a reversible metabolic cassette converting Ins(3,4,5,6)P4 into 5-InsP7 and back in a nucleotide-dependent manner. Thus, inositol tris/tetrakisphosphate kinase 1 is a nexus of bioenergetics status and inositol polyphosphate/diphosphoinositol phosphate metabolism. As such, it commands a role in plants that evolution has assigned to a different class of enzyme in mammalian cells. The findings and the methods described will enable a full appraisal of the role of diphosphoinositol phosphates in plants and particularly the relative contribution of reversible inositol phosphate hydroxykinase and inositol phosphate phosphokinase activities to plant physiology.

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Section: Inositol Phosphatesmentioning

confidence: 99%

An ATP-responsive metabolic cassette comprised of inositol tris/tetrakisphosphate kinase 1 (ITPK1) and inositol pentakisphosphate 2-kinase (IPK1) buffers diphosphosphoinositol phosphate levels

Whitfield

White

Sprigg

et al. 2020

Biochemical Journal

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“…The resulting benzyl-protected Ins(1,3,4,5,6)P 5 was deprotected by catalytic hydrogenolysis, and the product was purified to homogeneity by ion-exchange chromatography on Q-Sepharose Fast Flow resin, giving the pure triethylammonium salt of Ins(1,3,4,5,6)P 5 , which was fully characterized by 31 P and 1 H spectroscopy and accurately quantified by Effect of inositol pentakisphosphate on apoptosis E Piccolo et al total phosphate assay. Ins(1,4,5,6)P 4 and Ins(3,4,5,6)P 4 were synthesized in a similar way (Mills et al, 2003). pCis2-Myr-Akt was a kind gift of Dr MJ Quon (NIH, Bethesda, USA).…”

Section: Materials and Plasmidsmentioning

confidence: 99%

Inositol pentakisphosphate promotes apoptosis through the PI 3-K/Akt pathway

et al. 2004

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Phosphoinositide 3-kinase (PI 3-K) is implicated in a wide array of biological and pathophysiological responses, including tumorigenesis, invasion and metastasis, therefore specific inhibitors of the kinase may prove useful in cancer therapy. We propose that specific inositol polyphosphates have the potential to antagonize the activation of PI 3-K pathways by competing with the binding of PtdIns(3,4,5)P 3 to pleckstrin homology (PH) domains. Here we show that Ins(1,3,4,5,6)P 5 inhibits the serine phosphorylation and the kinase activity of Akt/PKB. As a consequence of this inhibition, Ins(1,3,4,5,6)P 5 induces apoptosis in ovarian, lung and breast cancer cells. Overexpression of constitutively active Akt protects SKBR-3 cells from Ins(1,3,4,5,6)P 5 -induced apoptosis. Furthermore, Ins(1,3,4,5,6)P 5 enhances the proapoptotic effect of cisplatin and etoposide in ovarian and lung cancer cells, respectively. These results support a role for Ins(1,3,4,5,6)P 5 as a specific inhibitor of the PI 3-K/Akt signalling pathway, that may sensitize cancer cells to the action of commonly used anticancer drugs.

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A Definitive Synthesis of D‐myo‐Inositol 1,4,5,6‐Tetrakisphosphate and Its Enantiomer D‐myo‐Inositol 3,4,5,6‐Tetrakisphosphate from a Novel Butane‐2,3‐diacetal‐Protected Inositol.

et al. 2004

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show abstract

A Definitive Synthesis ofD‐myo‐Inositol 1,4,5,6‐Tetrakisphosphate and Its EnantiomerD‐myo‐Inositol 3,4,5,6‐Tetrakisphosphate from a Novel Butane‐2,3‐diacetal‐Protected Inositol

Cited by 12 publications

References 39 publications

An ATP-responsive metabolic cassette comprised of inositol tris/tetrakisphosphate kinase 1 (ITPK1) and inositol pentakisphosphate 2-kinase (IPK1) buffers diphosphosphoinositol phosphate levels

An ATP-responsive metabolic cassette comprised of inositol tris/tetrakisphosphate kinase 1 (ITPK1) and inositol pentakisphosphate 2-kinase (IPK1) buffers diphosphosphoinositol phosphate levels

Inositol pentakisphosphate promotes apoptosis through the PI 3-K/Akt pathway

A Definitive Synthesis of D‐myo‐Inositol 1,4,5,6‐Tetrakisphosphate and Its Enantiomer D‐myo‐Inositol 3,4,5,6‐Tetrakisphosphate from a Novel Butane‐2,3‐diacetal‐Protected Inositol.

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