Synthesis of an azido-tagged low affinity ratiometric calcium sensor

Stuart T. Caldwell; Andrew G. Cairns; Marnie Olson; Susan Chalmers; Mairi Sandison; William Mullen; John G. McCarron; Richard C. Hartley

doi:10.1016/j.tet.2015.10.052

Synthesis of an azido-tagged low affinity ratiometric calcium sensor

Stuart T. Caldwell, Andrew G. Cairns, Marnie Olson, Susan Chalmers, Mairi Sandison, William Mullen, John G. McCarron, Richard C. Hartley (Lead / Corresponding author)

Drug Discovery Unit

Research output: Contribution to journal › Article › peer-review

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Abstract

Changes in high localised concentrations of Ca²⁺ ions are fundamental to cell signalling. The synthesis of a dual excitation, ratiometric calcium ion sensor with a K_d of 90 μM, is described. It is tagged with an azido group for bioconjugation, and absorbs in the blue/green and emits in the red region of the visible spectrum with a large Stokes shift. The binding modulating nitro group is introduced to the BAPTA core prior to construction of a benzofuran-2-yl carboxaldehyde by an allylation-oxidation-cyclisation sequence, which is followed by condensation with an azido-tagged thiohydantoin. The thiohydantoin unit has to be protected with an acetoxymethyl (AM) caging group to allow CuAAC click reaction and incorporation of the KDEL peptide endoplasmic reticulum (ER) retention sequence.

Original language	English
Pages (from-to)	9571-9578
Number of pages	8
Journal	Tetrahedron
Volume	71
Issue number	51
Early online date	20 Oct 2015
DOIs	https://doi.org/10.1016/j.tet.2015.10.052
Publication status	Published - 23 Dec 2015

Keywords

BAPTA
Bioorthogonal
Calcium
Fluorescence
Thiohydantoin

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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10.1016/j.tet.2015.10.052Licence: CC BY

Final Published VersionFinal published version, 605 KBLicence: CC BY

Cite this

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title = "Synthesis of an azido-tagged low affinity ratiometric calcium sensor",

abstract = "Changes in high localised concentrations of Ca2+ ions are fundamental to cell signalling. The synthesis of a dual excitation, ratiometric calcium ion sensor with a Kd of 90 μM, is described. It is tagged with an azido group for bioconjugation, and absorbs in the blue/green and emits in the red region of the visible spectrum with a large Stokes shift. The binding modulating nitro group is introduced to the BAPTA core prior to construction of a benzofuran-2-yl carboxaldehyde by an allylation-oxidation-cyclisation sequence, which is followed by condensation with an azido-tagged thiohydantoin. The thiohydantoin unit has to be protected with an acetoxymethyl (AM) caging group to allow CuAAC click reaction and incorporation of the KDEL peptide endoplasmic reticulum (ER) retention sequence.",

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author = "Caldwell, {Stuart T.} and Cairns, {Andrew G.} and Marnie Olson and Susan Chalmers and Mairi Sandison and William Mullen and McCarron, {John G.} and Hartley, {Richard C.}",

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AU - Caldwell, Stuart T.

AU - Cairns, Andrew G.

AU - Olson, Marnie

AU - Chalmers, Susan

AU - Sandison, Mairi

AU - Mullen, William

AU - McCarron, John G.

AU - Hartley, Richard C.

PY - 2015/12/23

Y1 - 2015/12/23

N2 - Changes in high localised concentrations of Ca2+ ions are fundamental to cell signalling. The synthesis of a dual excitation, ratiometric calcium ion sensor with a Kd of 90 μM, is described. It is tagged with an azido group for bioconjugation, and absorbs in the blue/green and emits in the red region of the visible spectrum with a large Stokes shift. The binding modulating nitro group is introduced to the BAPTA core prior to construction of a benzofuran-2-yl carboxaldehyde by an allylation-oxidation-cyclisation sequence, which is followed by condensation with an azido-tagged thiohydantoin. The thiohydantoin unit has to be protected with an acetoxymethyl (AM) caging group to allow CuAAC click reaction and incorporation of the KDEL peptide endoplasmic reticulum (ER) retention sequence.

AB - Changes in high localised concentrations of Ca2+ ions are fundamental to cell signalling. The synthesis of a dual excitation, ratiometric calcium ion sensor with a Kd of 90 μM, is described. It is tagged with an azido group for bioconjugation, and absorbs in the blue/green and emits in the red region of the visible spectrum with a large Stokes shift. The binding modulating nitro group is introduced to the BAPTA core prior to construction of a benzofuran-2-yl carboxaldehyde by an allylation-oxidation-cyclisation sequence, which is followed by condensation with an azido-tagged thiohydantoin. The thiohydantoin unit has to be protected with an acetoxymethyl (AM) caging group to allow CuAAC click reaction and incorporation of the KDEL peptide endoplasmic reticulum (ER) retention sequence.

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KW - Bioorthogonal

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KW - Fluorescence

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ER -

Synthesis of an azido-tagged low affinity ratiometric calcium sensor

Abstract

Keywords

ASJC Scopus subject areas

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