Research ExplorerPublicationsSynthesis of phosphonoacetate analogues of the second messen...

Synthesis of phosphonoacetate analogues of the second messenger adenosine 5'-diphosphate ribose (ADPR)

Standard

Synthesis of phosphonoacetate analogues of the second messenger adenosine 5'-diphosphate ribose (ADPR). / Baszczyňski, Ondřej; Watt, Joanna M; Rozewitz, Monika D; Fliegert, Ralf; Guse, Andreas H; Potter, Barry V L.

In: RSC ADV, Vol. 10, No. 3, 2020, p. 1776-1785.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Baszczyňski, O, Watt, JM, Rozewitz, MD, Fliegert, R, Guse, AH & Potter, BVL 2020, 'Synthesis of phosphonoacetate analogues of the second messenger adenosine 5'-diphosphate ribose (ADPR)', RSC ADV, vol. 10, no. 3, pp. 1776-1785. https://doi.org/10.1039/C9RA09284F

APA

Baszczyňski, O., Watt, J. M., Rozewitz, M. D., Fliegert, R., Guse, A. H., & Potter, B. V. L. (2020). Synthesis of phosphonoacetate analogues of the second messenger adenosine 5'-diphosphate ribose (ADPR). RSC ADV, 10(3), 1776-1785. https://doi.org/10.1039/C9RA09284F

Vancouver

Baszczyňski O, Watt JM, Rozewitz MD, Fliegert R, Guse AH, Potter BVL. Synthesis of phosphonoacetate analogues of the second messenger adenosine 5'-diphosphate ribose (ADPR). RSC ADV. 2020;10(3):1776-1785. https://doi.org/10.1039/C9RA09284F

Bibtex

@article{5a5d5f13391849aea513de6d7edc7672,
title = "Synthesis of phosphonoacetate analogues of the second messenger adenosine 5'-diphosphate ribose (ADPR)",
abstract = "Adenosine 5'-diphosphate ribose (ADPR) is an intracellular signalling molecule generated from nicotinamide adenine dinucleotide (NAD+). Synthetic ADPR analogues can shed light on the mechanism of activation of ADPR targets and their downstream effects. Such chemical biology studies, however, are often challenging due to the negatively charged pyrophosphate, also sensitive to cellular pyrophosphatases, and prior work on an initial ADPR target, the transient receptor potential cation channel TRPM2, showed complete pyrophosphate group replacement to be a step too far in maintaining biological activity. Thus, we designed ADPR analogues with just one of the negatively charged phosphate groups removed, by employing a phosphonoacetate linker. Synthesis of two novel phosphonoacetate ADPR analogues is described via tandem N,N'-dicyclohexylcarbodiimide coupling to phosphonoacetic acid. Neither analogue, however, showed significant agonist or antagonist activity towards TRPM2, underlining the importance of a complete pyrophosphate motif in activation of this particular receptor.",
author = "Ond{\v r}ej Baszczy{\v n}ski and Watt, {Joanna M} and Rozewitz, {Monika D} and Ralf Fliegert and Guse, {Andreas H} and Potter, {Barry V L}",
year = "2020",
doi = "10.1039/C9RA09284F",
language = "English",
volume = "10",
pages = "1776--1785",
journal = "RSC ADV",
issn = "2046-2069",
publisher = "Royal Society of Chemistry",
number = "3",

}

RIS

TY - JOUR

T1 - Synthesis of phosphonoacetate analogues of the second messenger adenosine 5'-diphosphate ribose (ADPR)

AU - Baszczyňski, Ondřej

AU - Watt, Joanna M

AU - Rozewitz, Monika D

AU - Fliegert, Ralf

AU - Guse, Andreas H

AU - Potter, Barry V L

PY - 2020

Y1 - 2020

N2 - Adenosine 5'-diphosphate ribose (ADPR) is an intracellular signalling molecule generated from nicotinamide adenine dinucleotide (NAD+). Synthetic ADPR analogues can shed light on the mechanism of activation of ADPR targets and their downstream effects. Such chemical biology studies, however, are often challenging due to the negatively charged pyrophosphate, also sensitive to cellular pyrophosphatases, and prior work on an initial ADPR target, the transient receptor potential cation channel TRPM2, showed complete pyrophosphate group replacement to be a step too far in maintaining biological activity. Thus, we designed ADPR analogues with just one of the negatively charged phosphate groups removed, by employing a phosphonoacetate linker. Synthesis of two novel phosphonoacetate ADPR analogues is described via tandem N,N'-dicyclohexylcarbodiimide coupling to phosphonoacetic acid. Neither analogue, however, showed significant agonist or antagonist activity towards TRPM2, underlining the importance of a complete pyrophosphate motif in activation of this particular receptor.

AB - Adenosine 5'-diphosphate ribose (ADPR) is an intracellular signalling molecule generated from nicotinamide adenine dinucleotide (NAD+). Synthetic ADPR analogues can shed light on the mechanism of activation of ADPR targets and their downstream effects. Such chemical biology studies, however, are often challenging due to the negatively charged pyrophosphate, also sensitive to cellular pyrophosphatases, and prior work on an initial ADPR target, the transient receptor potential cation channel TRPM2, showed complete pyrophosphate group replacement to be a step too far in maintaining biological activity. Thus, we designed ADPR analogues with just one of the negatively charged phosphate groups removed, by employing a phosphonoacetate linker. Synthesis of two novel phosphonoacetate ADPR analogues is described via tandem N,N'-dicyclohexylcarbodiimide coupling to phosphonoacetic acid. Neither analogue, however, showed significant agonist or antagonist activity towards TRPM2, underlining the importance of a complete pyrophosphate motif in activation of this particular receptor.

U2 - 10.1039/C9RA09284F

DO - 10.1039/C9RA09284F

M3 - SCORING: Journal article

C2 - 31934327

VL - 10

SP - 1776

EP - 1785

JO - RSC ADV

JF - RSC ADV

SN - 2046-2069

IS - 3

ER -