Synthesis and Biological Activity of Metabolically Stabilized Cyclopentyl Trisphosphate Analogues of D-myo-Ins(1,4,5)P3
We describe the synthesis of four novel metabolically stabilized analogues of Ins(1,4,5)P3 based on the known cyclopentane pentaol tris(phosphate) 2: tris(phosphorothioate) 3, tris(methylenephosphate) 4, tris(sulfonamide) 5, and tris(sulfate) 6. Of these analogues, only the tris(phosphorothioate) 3...
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| Veröffentlicht in: | ChemMedChem 2007-09, Vol.2 (9), p.1281-1289 |
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| creator | Zhang, Liuyin Huang, Wei Tanimura, Akihiko Morita, Takao Harihar, Sitaram DeWald, Daryll B. Prestwich, Glenn D. |
| description | We describe the synthesis of four novel metabolically stabilized analogues of Ins(1,4,5)P3 based on the known cyclopentane pentaol tris(phosphate) 2: tris(phosphorothioate) 3, tris(methylenephosphate) 4, tris(sulfonamide) 5, and tris(sulfate) 6. Of these analogues, only the tris(phosphorothioate) 3 and parent tris(phosphate) 2 bound to the type I InsP3R construct. In addition, both the tris(phosphorothioate) 3 and parent tris(phosphate) 2 elicited calcium release in MDA MB‐435 breast cancer cells. The Ins(1,4,5)P3 agonist activities of these two compounds can be rationalized on the basis of computational docking of the ligands to the binding domain of the type I InsP3R.
Ins(1,4,5)P3 analogues: Four phosphatase‐resistant analogues of Ins(1,4,5)P3 were synthesized and evaluated. Tris(phosphorothioate) 3 and the parent tris(phosphate) bound to an InsP3R construct in vitro and elicited calcium release in breast cancer cells. The agonist activity was rationalized by computational docking of the ligands to the binding domain of the InsP3R. |
| doi_str_mv | 10.1002/cmdc.200700071 |
| format | Article |
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Ins(1,4,5)P3 analogues: Four phosphatase‐resistant analogues of Ins(1,4,5)P3 were synthesized and evaluated. Tris(phosphorothioate) 3 and the parent tris(phosphate) bound to an InsP3R construct in vitro and elicited calcium release in breast cancer cells. The agonist activity was rationalized by computational docking of the ligands to the binding domain of the InsP3R.</description><identifier>ISSN: 1860-7179</identifier><identifier>EISSN: 1860-7187</identifier><identifier>DOI: 10.1002/cmdc.200700071</identifier><identifier>PMID: 17589888</identifier><language>eng</language><publisher>Weinheim: WILEY-VCH Verlag</publisher><subject>calcium ; Crystallography, X-Ray ; docking ; Inositol 1,4,5-Trisphosphate - analogs & derivatives ; Inositol 1,4,5-Trisphosphate - chemical synthesis ; Inositol 1,4,5-Trisphosphate - pharmacology ; Magnetic Resonance Spectroscopy ; Organophosphorus Compounds - chemical synthesis ; Organophosphorus Compounds - chemistry ; Organophosphorus Compounds - pharmacology ; phosphorothioates ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; sulfates ; sulfonamides</subject><ispartof>ChemMedChem, 2007-09, Vol.2 (9), p.1281-1289</ispartof><rights>Copyright © 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcmdc.200700071$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcmdc.200700071$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27929,27930,45579,45580</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17589888$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Liuyin</creatorcontrib><creatorcontrib>Huang, Wei</creatorcontrib><creatorcontrib>Tanimura, Akihiko</creatorcontrib><creatorcontrib>Morita, Takao</creatorcontrib><creatorcontrib>Harihar, Sitaram</creatorcontrib><creatorcontrib>DeWald, Daryll B.</creatorcontrib><creatorcontrib>Prestwich, Glenn D.</creatorcontrib><title>Synthesis and Biological Activity of Metabolically Stabilized Cyclopentyl Trisphosphate Analogues of D-myo-Ins(1,4,5)P3</title><title>ChemMedChem</title><addtitle>ChemMedChem</addtitle><description>We describe the synthesis of four novel metabolically stabilized analogues of Ins(1,4,5)P3 based on the known cyclopentane pentaol tris(phosphate) 2: tris(phosphorothioate) 3, tris(methylenephosphate) 4, tris(sulfonamide) 5, and tris(sulfate) 6. Of these analogues, only the tris(phosphorothioate) 3 and parent tris(phosphate) 2 bound to the type I InsP3R construct. In addition, both the tris(phosphorothioate) 3 and parent tris(phosphate) 2 elicited calcium release in MDA MB‐435 breast cancer cells. The Ins(1,4,5)P3 agonist activities of these two compounds can be rationalized on the basis of computational docking of the ligands to the binding domain of the type I InsP3R.
Ins(1,4,5)P3 analogues: Four phosphatase‐resistant analogues of Ins(1,4,5)P3 were synthesized and evaluated. Tris(phosphorothioate) 3 and the parent tris(phosphate) bound to an InsP3R construct in vitro and elicited calcium release in breast cancer cells. The agonist activity was rationalized by computational docking of the ligands to the binding domain of the InsP3R.</description><subject>calcium</subject><subject>Crystallography, X-Ray</subject><subject>docking</subject><subject>Inositol 1,4,5-Trisphosphate - analogs & derivatives</subject><subject>Inositol 1,4,5-Trisphosphate - chemical synthesis</subject><subject>Inositol 1,4,5-Trisphosphate - pharmacology</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Organophosphorus Compounds - chemical synthesis</subject><subject>Organophosphorus Compounds - chemistry</subject><subject>Organophosphorus Compounds - pharmacology</subject><subject>phosphorothioates</subject><subject>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</subject><subject>sulfates</subject><subject>sulfonamides</subject><issn>1860-7179</issn><issn>1860-7187</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFUMtOwzAQtBCIR-HKEfkIUlPsOImdY0lpKeJR1PK4WZvYAYObVHVKCV9PqkI5jHZnd2YOg9AxJR1KiH-eTVXW8QnhpAHdQvtURMTjVPDtzc7jPXTg3DshQSCo2EV7lIciFkLso-W4Lqo37YzDUCh8YUpbvpoMLO5mlfk0VY3LHN_qCtLSru62xuOGGGu-tcJJndlypouqtngyN272VjaASuNuAU3SQruVv-dN69IbFu6UtoN2eDZih2gnB-v00e9socf-5SS58m7uB8Oke-MZKij1UgZcaQJRrjiwUKdhxII0VxnLKVWZ9pXgKoaAE6FjldLMB4giABFDGqk8Zy10ss6dLdKpVnI2N1OY1_KvgUYQrwVLY3X9_ydy1a9c9Ss3_crktpdsWOP11l7jKv218cL8Q0ac8VA-3w3k9VPfZy-jBxmyHxwagCM</recordid><startdate>20070910</startdate><enddate>20070910</enddate><creator>Zhang, Liuyin</creator><creator>Huang, Wei</creator><creator>Tanimura, Akihiko</creator><creator>Morita, Takao</creator><creator>Harihar, Sitaram</creator><creator>DeWald, Daryll B.</creator><creator>Prestwich, Glenn D.</creator><general>WILEY-VCH Verlag</general><general>WILEY‐VCH Verlag</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>20070910</creationdate><title>Synthesis and Biological Activity of Metabolically Stabilized Cyclopentyl Trisphosphate Analogues of D-myo-Ins(1,4,5)P3</title><author>Zhang, Liuyin ; Huang, Wei ; Tanimura, Akihiko ; Morita, Takao ; Harihar, Sitaram ; DeWald, Daryll B. ; Prestwich, Glenn D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-i1811-b3a7de0a6fd7a35eb5634bfdc3f11dce2d87d9a4708e9db1c2aa66aa89ab6dff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>calcium</topic><topic>Crystallography, X-Ray</topic><topic>docking</topic><topic>Inositol 1,4,5-Trisphosphate - analogs & derivatives</topic><topic>Inositol 1,4,5-Trisphosphate - chemical synthesis</topic><topic>Inositol 1,4,5-Trisphosphate - pharmacology</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Organophosphorus Compounds - chemical synthesis</topic><topic>Organophosphorus Compounds - chemistry</topic><topic>Organophosphorus Compounds - pharmacology</topic><topic>phosphorothioates</topic><topic>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</topic><topic>sulfates</topic><topic>sulfonamides</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Liuyin</creatorcontrib><creatorcontrib>Huang, Wei</creatorcontrib><creatorcontrib>Tanimura, Akihiko</creatorcontrib><creatorcontrib>Morita, Takao</creatorcontrib><creatorcontrib>Harihar, Sitaram</creatorcontrib><creatorcontrib>DeWald, Daryll B.</creatorcontrib><creatorcontrib>Prestwich, Glenn D.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>ChemMedChem</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Liuyin</au><au>Huang, Wei</au><au>Tanimura, Akihiko</au><au>Morita, Takao</au><au>Harihar, Sitaram</au><au>DeWald, Daryll B.</au><au>Prestwich, Glenn D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and Biological Activity of Metabolically Stabilized Cyclopentyl Trisphosphate Analogues of D-myo-Ins(1,4,5)P3</atitle><jtitle>ChemMedChem</jtitle><addtitle>ChemMedChem</addtitle><date>2007-09-10</date><risdate>2007</risdate><volume>2</volume><issue>9</issue><spage>1281</spage><epage>1289</epage><pages>1281-1289</pages><issn>1860-7179</issn><eissn>1860-7187</eissn><abstract>We describe the synthesis of four novel metabolically stabilized analogues of Ins(1,4,5)P3 based on the known cyclopentane pentaol tris(phosphate) 2: tris(phosphorothioate) 3, tris(methylenephosphate) 4, tris(sulfonamide) 5, and tris(sulfate) 6. Of these analogues, only the tris(phosphorothioate) 3 and parent tris(phosphate) 2 bound to the type I InsP3R construct. In addition, both the tris(phosphorothioate) 3 and parent tris(phosphate) 2 elicited calcium release in MDA MB‐435 breast cancer cells. The Ins(1,4,5)P3 agonist activities of these two compounds can be rationalized on the basis of computational docking of the ligands to the binding domain of the type I InsP3R.
Ins(1,4,5)P3 analogues: Four phosphatase‐resistant analogues of Ins(1,4,5)P3 were synthesized and evaluated. Tris(phosphorothioate) 3 and the parent tris(phosphate) bound to an InsP3R construct in vitro and elicited calcium release in breast cancer cells. The agonist activity was rationalized by computational docking of the ligands to the binding domain of the InsP3R.</abstract><cop>Weinheim</cop><pub>WILEY-VCH Verlag</pub><pmid>17589888</pmid><doi>10.1002/cmdc.200700071</doi><tpages>9</tpages></addata></record> |
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| subjects | calcium Crystallography, X-Ray docking Inositol 1,4,5-Trisphosphate - analogs & derivatives Inositol 1,4,5-Trisphosphate - chemical synthesis Inositol 1,4,5-Trisphosphate - pharmacology Magnetic Resonance Spectroscopy Organophosphorus Compounds - chemical synthesis Organophosphorus Compounds - chemistry Organophosphorus Compounds - pharmacology phosphorothioates Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization sulfates sulfonamides |
| title | Synthesis and Biological Activity of Metabolically Stabilized Cyclopentyl Trisphosphate Analogues of D-myo-Ins(1,4,5)P3 |
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