Synthesis and Biological Activity of Metabolically Stabilized Cyclopentyl Trisphosphate Analogues of <scp>D</scp>‐<i>myo‐</i>Ins(1,4,5)P<sub>3</sub>

Zhang, Liuyin; Huang, Wei; Tanimura, Akihiko; Mitsui, Takao; Harihar, Sitaram; DeWald, Daryll B.; Prestwich, Glenn D.

doi:10.1002/cmdc.200700071

Cited by 15 publications

(6 citation statements)

References 33 publications

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“…Prestwich et al has reported the sulfate-and sulfamate-containing cyclopentyl InsP 3 derivatives 56 and 57. 93 These compounds were shown not to bind InsP 3 receptors, which is consistent with the data of Westerduin et al 92 Although some of these compounds show no activity at their target receptors, the data obtained are collectively useful in determining the subtle structure-activity relationships of compounds that act at the InsP 3 receptors.…”

Section: Boranophosphatessupporting

confidence: 82%

The use of phosphate bioisosteres in medicinal chemistry and chemical biology

et al. 2012

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Phosphate and pyrophosphate groups play a central role in cellular signalling and consequently are of great interest to both medicinal chemists and chemical biologists. However, the design of molecules that can interfere with phosphate-based processes is recognised as a significant challenge, especially when the resulting compounds must show good cellular penetration and stability. Herein, we have reviewed the full range of phosphate bioisosteres currently reported and provided the context of their deployment. We aim to provide a useful reference for medicinal chemists and chemical biologists who are engaged in the design of molecules that target phosphate-binding proteins.

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Section: Boranophosphatessupporting

confidence: 82%

The use of phosphate bioisosteres in medicinal chemistry and chemical biology

et al. 2012

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“…In addition, it has been reported that structural differences in the suppressor domains contribute to functional diversity in ligand sensitivity among IP 3 R isoforms (20), assuming that the ligand-binding properties of the LIBRAv series reflect this feature of IP 3 R isoforms. We previously reported a method using LIBRA for determining IP 3 R ligands (21), and we identified novel ligands of IP 3 Rs from newly synthesized cyclopentane derivatives (22). This method could be extended easily for identifying subtype-specific ligands of IP 3 Rs by using a series of new LIBRAv variants.…”

Section: Resultsmentioning

confidence: 99%

Use of Fluorescence Resonance Energy Transfer-based Biosensors for the Quantitative Analysis of Inositol 1,4,5-Trisphosphate Dynamics in Calcium Oscillations

Tanimura

Mitsui

Nezu

et al. 2009

Journal of Biological Chemistry

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(7,8). On the other hand, oscillatory changes in [IP 3 ] i have been suggested by the observed cyclical translocation of a GFPtagged pleckstrin homology domain of PLC-␦ (GFP-PHD) (9, 10). However, in other experiments using more specific IP 3 biosensors, IP 3 was shown to accumulate gradually with little or no fluctuation during Ca 2ϩ oscillations (11). These discrepant observations may be attributable to differences between various IP 3 biosensors and a lack of quantitation.There are two types of IP 3 biosensors, GFP-PHD and IP 3 Rbased FRET sensors. GFP-PHD binds to both PIP 2 and IP 3 ; thus it has been thought that changes in [IP 3 ] i could be monitored indirectly by the release of membrane-bound GFP-PHD (9). IP 3 R-based FRET biosensors consist of the ligand-binding domain of IP 3 R and a pair of fluorescent proteins, cyan fluorescent protein and yellow fluorescent protein. Since the successful monitoring of IP 3 with LIBRA (12), the first IP 3 R-based FRET biosensor, several different groups have used similar biosensors for IP 3 monitoring (11,13,14). In principle, quantitative measurements of [IP 3 ] i are not possible with GFP-PHD. In addition, it is recognized that GFP-PHD may be released from the plasma membrane by decreases in available PIP 2 (15), which could be attributed to PIP 2 hydrolysis or the occupation by other molecules. IP 3 R-based FRET biosensors offer significant benefits for monitoring IP 3 based on their high selectivity for IP 3 and ratiometric measurement.In this study, we developed a series of improved IP 3 biosensors that exhibit high pH stability and varying IP 3 affinities. They also possess higher selectively and afford a larger dynamic range than that of original LIBRA. In combination with these * This work was supported by Grant-in-aid for Scientific Research 16390532 (to A. T.), by HAITEKU (2007) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Japan Science and Technology Agency. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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“…Indeed, we demonstrated that PtdIns(3)PT had reduced binding activity for cognate PtdIns(3)P-selective FYVE and PX domain binding proteins, which was attributable to reduced H-bonding (18). We also observed that a PT analogue of PtdIns(5)P was a long-lived agonist for chromatin remodeling (19), and a tris(PT) cyclopentyl analogue (20) of Ins(1,4,5)P 3 was a long-lived agonist activities for the IP 3 receptor. We hypothesized that a 5-PT and 5-MP analogues of PtdIns(3,4,5)P 3 could be either antagonists or long-lived PtdIns(3,4,5)P 3 agonists, as they would be more slowly dephosphorylated by the 5-phosphatase SHIP and could potentially block the normal receptor-mediated signaling involving PtdIns(3,4,5)P 3 .…”

Section: Introductionmentioning

confidence: 78%

5‐Stabilized Phosphatidylinositol 3,4,5‐Trisphosphate Analogues Bind Grp1 PH, Inhibit Phosphoinositide Phosphatases, and Block Neutrophil Migration

Zhang

Kutateladze

et al. 2010

ChemBioChem

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Metabolically-stabilized analogues of PtdIns(3,4,5)P3 have shown long-lived agonist activity for cellular events and selective inhibition of lipid phosphatase activity. We describe an efficient asymmetric synthesis of two 5-phosphatase resistant analogues of PtdIns(3,4,5)P3, the 5-methylene phosphonate (MP) and 5-phosphorothioate (PT). Furthermore, we illustrate the biochemical and biological activities of a total of five stabilized PtdIns(3,4,5)P3 analogues in four contexts. First, the relative binding affinities of the 3-MP, 3-PT, 5-MP, 5-PT, and 3,4,5-PT3 analogues to the Grp1 PH domain are shown, as determined by NMR. Second, the enzymology of the five analogues is explored, showing the relative efficiency of inhibition of SHIP1, SHIP2, and PTEN, as well as the greatly reduced ability of these phosphatases to process these analogues as substrates as compared to PtdIns(3,4,5)P3. Third, exogenously-delivered analogues severely impair complement factor C5a-mediated polarization and migration of murine neutrophils. Finally, the new analogues show long-lived agonist activity in mimicking insulin action in sodium transport in A6 cells.

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Synthesis and Biological Activity of Metabolically Stabilized Cyclopentyl Trisphosphate Analogues of D‐myo‐Ins(1,4,5)P₃

Cited by 15 publications

References 33 publications

The use of phosphate bioisosteres in medicinal chemistry and chemical biology

The use of phosphate bioisosteres in medicinal chemistry and chemical biology

Use of Fluorescence Resonance Energy Transfer-based Biosensors for the Quantitative Analysis of Inositol 1,4,5-Trisphosphate Dynamics in Calcium Oscillations

5‐Stabilized Phosphatidylinositol 3,4,5‐Trisphosphate Analogues Bind Grp1 PH, Inhibit Phosphoinositide Phosphatases, and Block Neutrophil Migration

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Synthesis and Biological Activity of Metabolically Stabilized Cyclopentyl Trisphosphate Analogues of D‐myo‐Ins(1,4,5)P3

Cited by 15 publications

References 33 publications

The use of phosphate bioisosteres in medicinal chemistry and chemical biology

The use of phosphate bioisosteres in medicinal chemistry and chemical biology

Use of Fluorescence Resonance Energy Transfer-based Biosensors for the Quantitative Analysis of Inositol 1,4,5-Trisphosphate Dynamics in Calcium Oscillations

5‐Stabilized Phosphatidylinositol 3,4,5‐Trisphosphate Analogues Bind Grp1 PH, Inhibit Phosphoinositide Phosphatases, and Block Neutrophil Migration

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Synthesis and Biological Activity of Metabolically Stabilized Cyclopentyl Trisphosphate Analogues of D‐myo‐Ins(1,4,5)P₃