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

Baszczynski Ondrej; Watt Joanna M.; Rozewitz Monika D.; Fliegert Ralf; Guse Andreas H.; Potter Barry V. L.

首页> 外文期刊>RSC Advances >Synthesis of phosphonoacetate analogues of the second messenger adenosine 5 '-diphosphate ribose (ADPR)

【24h】

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

机译：第二信使腺苷5'-二二磷酸核糖糖（ADPR）的膦酰乙酸酯类似物的合成

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相似文献
相关主题

摘要

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 that is also sensitive to cellular pyrophosphatases. 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.

机译：腺苷5'-二磷酸核糖（ADPR）是由烟酰胺腺嘌呤二核苷酸产生的细胞内信号传递分子（NAD（+））。合成ADPR类似物可以在激活ADPR靶标的机制和下游效应上脱光。然而，这种化学生物学研究通常是由于对细胞焦磷酸酶敏感的带负电的焦磷酸盐而挑战。在初始ADPR靶开始上的工作，瞬态受体电位阳离子通道TRPM2显示出完全的焦磷酸酯基团替代物在维持生物活性方面是较远的步骤。因此，我们通过使用膦酰乙酸酯接头，设计了仅具有除去负电荷的磷酸盐基团之一的ADPR类似物。通过串联N，N'-二环己基碳二亚胺偶联与膦酸乙酯，描述了两种新型膦酰乙酸酯ADPR类似物的合成。然而，既不是类似物向TRPM2显示出显着的激动剂或拮抗剂活性，强调了完全焦磷酸酯基序在该特定受体的活化中的重要性。

著录项

来源
《RSC Advances》 |2020年第3期|共10页
作者
Baszczynski Ondrej; Watt Joanna M.; Rozewitz Monika D.; Fliegert Ralf; Guse Andreas H.; Potter Barry V. L.;
展开▼
作者单位

Univ Bath Dept Pharm &

Pharmacol Wolfson Lab Med Chem Bath BA2 7AY Avon England;

Univ Oxford Dept Pharmacol Med Chem &

Drug Discovery Mansfield Rd Oxford OX1 3QT England;

Univ Med Ctr Hamburg Eppendorf Dept Biochem &

Mol Cell Biol Calcium Signalling Grp Martinistr 52 D-20246 Hamburg Germany;

Univ Med Ctr Hamburg Eppendorf Dept Biochem &

Mol Cell Biol Calcium Signalling Grp Martinistr 52 D-20246 Hamburg Germany;

Univ Med Ctr Hamburg Eppendorf Dept Biochem &

Mol Cell Biol Calcium Signalling Grp Martinistr 52 D-20246 Hamburg Germany;

Univ Oxford Dept Pharmacol Med Chem &

Drug Discovery Mansfield Rd Oxford OX1 3QT England;

展开▼
收录信息
原文格式 PDF
正文语种 eng
中图分类化学;
关键词

相似文献

外文文献
中文文献
专利

1. Synthesis of phosphonoacetate analogues of the second messenger adenosine 5 '-diphosphate ribose (ADPR) [J] . Baszczynski Ondrej, Watt Joanna M., Rozewitz Monika D., RSC Advances . 2020,第3期

机译：第二信使腺苷5'-二二磷酸核糖糖（ADPR）的膦酰乙酸酯类似物的合成
2. Synthesis of Terminal Ribose Analogues of Adenosine 5 '-Diphosphate Ribose as Probes for the Transient Receptor Potential Cation Channel TRPM2 [J] . Baszczynski Ondrej, Watt Joanna M., Rozewitz Monika D., The Journal of Organic Chemistry . 2019,第10期

机译：腺苷5' - 二磷酸核糖糖的末端核糖类似物的合成作为瞬态受体电位阳离子通道TRPM2的探针
3. Synthesis of cyclic adenosine 5'-diphosphate ribose analogues: a C2' endo/syn 'southern' ribose conformation underlies activity at the sea urchin cADPR receptor [J] . Christelle Moreau, Gloria A. Ashamu, Victoria C. Bailey, Organic & biomolecular chemistry . 2011,第1期

机译：环状腺苷5'-二磷酸核糖类似物的合成：C2'内/ Syn'南部'核糖构象奠定了海胆cADPR受体的活性基础
4. Design, Synthesis, and Cytoprotective Effect of 2-Aminothiazole Analogues as Potent Poly(ADP-Ribose) Polymerase-1 Inhibitors [C] . Wen-Ting Zhang, Gang-Ying Chen, Yi-Jing Zhu, ICMSI;International conference of molecular simulations and applied informatics technologies . 2010

机译：2-氨基噻唑类似物作为强力聚（ADP-核糖）聚合酶-1抑制剂的设计，合成和细胞保护作用
5. Discovery, evolution, and clinical use of poly(adenosine-diphosphate-ribose)polymerase-1,2 (PARP-1,2) inhibitors. [D] . Jang, KyungMin. 2012

机译：聚（腺苷二磷酸核糖）聚合酶-1，2（PARP-1，2）抑制剂的发现，发展和临床应用。
6. Second messenger analogues highlight unexpected substrate sensitivity of CD38: total synthesis of the hybrid L-cyclic inosine 5′-diphosphate ribose [O] . Joanna M. Watt, Richard Graeff, Mark P. Thomas, -1

机译：第二信使类似物突显了CD38的意外底物敏感性：杂合 L-环肌苷5-二磷酸核糖的全合成
7. Synthesis of phosphonoacetate analogues of the second messenger adenosine 5′-diphosphate ribose (ADPR) [O] . Ondřej Baszczyňski, Joanna M. Watt, Monika D. Rozewitz, 2020

机译：第二信使腺苷5'-二磷酸核糖糖（ADPR）的膦酰乙酸盐类似物的合成
8. Mechanism of Action of 'Pseudomonas aeruginosa' Exotoxin A in Experimental Mouse Infections. Adenosine Diphosphate Ribosylation of Elongation Factor 2. [R] . Pavlovskis, O. R., Iglewski, B. H., Pollack, M. 1977

机译：“铜绿假单胞菌”外毒素a在实验性小鼠感染中的作用机制。延长因子2的腺苷二磷酸核糖基化。

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

摘要

著录项

相似文献

相关主题

期刊订阅