Membrane-permeant esters of inositol polyphosphates, chemical syntheses and biological applications

doi:10.1016/S0040-4020(97)00714-X

Tetrahedron

Volume 53, Issue 35, 1 September 1997, Pages 12017-12040

https://doi.org/10.1016/S0040-4020(97)00714-X Get rights and content

Abstract

Membrane-permeant derivatives of inositol polyphosphates are useful tools for biological studies. Racemic 2,3,6-tri-O-butyryl-myo-inositol 1,4,5-trisphosphate hexakis(acetoxymethyl) ester( $Bt_{3} IP_{3} AM$ ), myo-inositol 1,4,5-trisphosphate hexakis(acetoxymethyl) ester ( $IP_{3} AM$ ), hexakis(propionyloxymethyl) ester ( $IP_{3} PM$ ) and hexakis(butyryloxymethyl) ester ( $IP_{3} BM$ ) were therefore synthesized. Whereas extracellular application of up to 200 μM of $Bt_{3} IP_{3} AM$ or $IP_{3} AM$ to 1321N1 astrocytoma cells failed to mobilize internal calcium, $IP_{3} PM$ and $IP_{3} BM$ released internal calcium at concentrations as low as 20 μM and 2 μM, respectively.

Five membrane-permeant esters of inositol polyphosphates were synthesized and their biological activities were evaluated in intact cells.

Membrane-permeant derivatives of inositol polyphosphates are useful tools for biological studies. $IP_{3} AM$ , $0IP_{3} PM$ , $IP_{3} BM$ , $Bt_{3} IP_{3} AM$ , and $Bt_{2} IP_{4} AM$ were therefore synthesized. Whereas extracellular application of up to 200 μM of $Bt_{3} IP_{3} AM$ or $IP_{3} AM$ to 1321N1 astrocytoma cells failed to mobilize internal calcium, $IP_{3} PM$ and $IP_{3} BM$ were effective at concentrations as low as 20 μM and 2 μM, respectively.

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^☆: Funding was provided by the Howard Hughes Medical Institute and NIH grant NS27177 to R. Y. Tsien

⁴: Current address: Universität Breman, UFT, Institut für Organische Chemie, 28359 Bremen, Germany

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Membrane-permeant esters of inositol polyphosphates, chemical syntheses and biological applications☆

Abstract

J. Biol. Chem.

J. Biol. Chem.

Bioorg. Chem.

Biochem. Pharmacol.

Tetrahedron Lett.

Cell Calcium

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

Brain Res.

J. Biol. Chem.

FEBS Lett.

J. Biol. Chem.

Methods Cell Biol.

Methods in Enzymology

Nature

Nature

Nature

Mol. Pharmacol.

Mol. Pharmacol.

Nature

J. Chem. Soc.