Bis-phenanthroline derivatives as suitable scaffolds for effective G-quadruplex recognitionElectronic supplementary information (ESI) available: Additional data. See DOI: 10.1039/c0dt00038h

Selective recognition of DNA folding is central to multiple biological and pharmacological applications aimed at precise targeting of distinct genomic regions. Here, we focused on the recognition of physiologically relevant G-quadruplex (G-4) structures by bis-phenanthroline (bis-Phen) ligands conta...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Bianco, S, Musetti, C, Waldeck, A, Sparapani, S, Seitz, J. D, Krapcho, A. P, Palumbo, M, Sissi, C
Format: Artikel
Sprache:eng
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 5841
container_issue 25
container_start_page 5833
container_title
container_volume 39
creator Bianco, S
Musetti, C
Waldeck, A
Sparapani, S
Seitz, J. D
Krapcho, A. P
Palumbo, M
Sissi, C
description Selective recognition of DNA folding is central to multiple biological and pharmacological applications aimed at precise targeting of distinct genomic regions. Here, we focused on the recognition of physiologically relevant G-quadruplex (G-4) structures by bis-phenanthroline (bis-Phen) ligands containing two Phen moieties covalently linked through an amine or thioether bond. The transition metal ions Mn 2+ , Ni 2+ , Cu 2+ , and the biologically relevant Mg 2+ and Zn 2+ efficiently form 1 : 1 bis-Phen complexes characterised by a large planar structure fit to successfully recognise G-quartet arrangements. Interestingly, metal ion complexation dramatically affects ligand-stabilising effects on G-quadruplex, the melting temperature of the folded structure being increased up to 30 °C at ligand concentrations as low as 1 μM in the presence of Ni 2+ and Cu 2+ . In addition, the test complexes were able to induce G-4 formation from essentially unfolded G-rich sequences even in the absence of K + ions as shown by gel shift and circular dichroism experiments. In line with their G-4 stabilising properties bis-Phen complexes are effective inhibitors of telomerase activity, Ni( ii ) complexes being effective in the sub-micromolar range. This is combined with lack of unselective DNA-damaging activity and short-term cellular toxicity, which makes the novel compounds (above all their Ni( ii ) complexes) interesting antiproliferative drug leads. Transition metal ions Mn 2+ , Ni 2+ , Cu 2+ , and the biologically relevant Mg 2+ and Zn 2+ efficiently form 1 : 1 bis-Phen complexes characterised by a large planar structure fit to successfully recognise G-quartet arrangements.
doi_str_mv 10.1039/c0dt00038h
format Article
fullrecord <record><control><sourceid>rsc</sourceid><recordid>TN_cdi_rsc_primary_c0dt00038h</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>c0dt00038h</sourcerecordid><originalsourceid>FETCH-rsc_primary_c0dt00038h3</originalsourceid><addsrcrecordid>eNqFj7FOwzAQhi0EEqWwsCMdGwwpTlIo7UYhhU4MZY8O-0yMHDvYTgQPx7uRIAQDEkx30vfd_-sYO0z5JOX5_ExwGTnn-WW1xUbpdDZL5lk-3f7es4tdthfCM-dZxs-zEXtf6pA0FVm0sfLOaEsgyesOo-4oAAYIrY74aAiCQKWckQGU80BKkRgkuE1eWpS-bQy9gifhnqyO2tnC9IJ3Vos-o-lpTTaifwNt-4AaBwdOis36FLBDbYaSBVxJ-XmNBiRGnMCGCG7u1wv4_eQ-21FoAh18zTE7WhUP13eJD6JsvK77tvJHz__nx3_xspEq_wBQTHKr</addsrcrecordid><sourcetype>Enrichment Source</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Bis-phenanthroline derivatives as suitable scaffolds for effective G-quadruplex recognitionElectronic supplementary information (ESI) available: Additional data. See DOI: 10.1039/c0dt00038h</title><source>Royal Society Of Chemistry Journals</source><source>Alma/SFX Local Collection</source><creator>Bianco, S ; Musetti, C ; Waldeck, A ; Sparapani, S ; Seitz, J. D ; Krapcho, A. P ; Palumbo, M ; Sissi, C</creator><creatorcontrib>Bianco, S ; Musetti, C ; Waldeck, A ; Sparapani, S ; Seitz, J. D ; Krapcho, A. P ; Palumbo, M ; Sissi, C</creatorcontrib><description>Selective recognition of DNA folding is central to multiple biological and pharmacological applications aimed at precise targeting of distinct genomic regions. Here, we focused on the recognition of physiologically relevant G-quadruplex (G-4) structures by bis-phenanthroline (bis-Phen) ligands containing two Phen moieties covalently linked through an amine or thioether bond. The transition metal ions Mn 2+ , Ni 2+ , Cu 2+ , and the biologically relevant Mg 2+ and Zn 2+ efficiently form 1 : 1 bis-Phen complexes characterised by a large planar structure fit to successfully recognise G-quartet arrangements. Interestingly, metal ion complexation dramatically affects ligand-stabilising effects on G-quadruplex, the melting temperature of the folded structure being increased up to 30 °C at ligand concentrations as low as 1 μM in the presence of Ni 2+ and Cu 2+ . In addition, the test complexes were able to induce G-4 formation from essentially unfolded G-rich sequences even in the absence of K + ions as shown by gel shift and circular dichroism experiments. In line with their G-4 stabilising properties bis-Phen complexes are effective inhibitors of telomerase activity, Ni( ii ) complexes being effective in the sub-micromolar range. This is combined with lack of unselective DNA-damaging activity and short-term cellular toxicity, which makes the novel compounds (above all their Ni( ii ) complexes) interesting antiproliferative drug leads. Transition metal ions Mn 2+ , Ni 2+ , Cu 2+ , and the biologically relevant Mg 2+ and Zn 2+ efficiently form 1 : 1 bis-Phen complexes characterised by a large planar structure fit to successfully recognise G-quartet arrangements.</description><identifier>ISSN: 1477-9226</identifier><identifier>EISSN: 1477-9234</identifier><identifier>DOI: 10.1039/c0dt00038h</identifier><language>eng</language><creationdate>2010-06</creationdate><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Bianco, S</creatorcontrib><creatorcontrib>Musetti, C</creatorcontrib><creatorcontrib>Waldeck, A</creatorcontrib><creatorcontrib>Sparapani, S</creatorcontrib><creatorcontrib>Seitz, J. D</creatorcontrib><creatorcontrib>Krapcho, A. P</creatorcontrib><creatorcontrib>Palumbo, M</creatorcontrib><creatorcontrib>Sissi, C</creatorcontrib><title>Bis-phenanthroline derivatives as suitable scaffolds for effective G-quadruplex recognitionElectronic supplementary information (ESI) available: Additional data. See DOI: 10.1039/c0dt00038h</title><description>Selective recognition of DNA folding is central to multiple biological and pharmacological applications aimed at precise targeting of distinct genomic regions. Here, we focused on the recognition of physiologically relevant G-quadruplex (G-4) structures by bis-phenanthroline (bis-Phen) ligands containing two Phen moieties covalently linked through an amine or thioether bond. The transition metal ions Mn 2+ , Ni 2+ , Cu 2+ , and the biologically relevant Mg 2+ and Zn 2+ efficiently form 1 : 1 bis-Phen complexes characterised by a large planar structure fit to successfully recognise G-quartet arrangements. Interestingly, metal ion complexation dramatically affects ligand-stabilising effects on G-quadruplex, the melting temperature of the folded structure being increased up to 30 °C at ligand concentrations as low as 1 μM in the presence of Ni 2+ and Cu 2+ . In addition, the test complexes were able to induce G-4 formation from essentially unfolded G-rich sequences even in the absence of K + ions as shown by gel shift and circular dichroism experiments. In line with their G-4 stabilising properties bis-Phen complexes are effective inhibitors of telomerase activity, Ni( ii ) complexes being effective in the sub-micromolar range. This is combined with lack of unselective DNA-damaging activity and short-term cellular toxicity, which makes the novel compounds (above all their Ni( ii ) complexes) interesting antiproliferative drug leads. Transition metal ions Mn 2+ , Ni 2+ , Cu 2+ , and the biologically relevant Mg 2+ and Zn 2+ efficiently form 1 : 1 bis-Phen complexes characterised by a large planar structure fit to successfully recognise G-quartet arrangements.</description><issn>1477-9226</issn><issn>1477-9234</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid/><recordid>eNqFj7FOwzAQhi0EEqWwsCMdGwwpTlIo7UYhhU4MZY8O-0yMHDvYTgQPx7uRIAQDEkx30vfd_-sYO0z5JOX5_ExwGTnn-WW1xUbpdDZL5lk-3f7es4tdthfCM-dZxs-zEXtf6pA0FVm0sfLOaEsgyesOo-4oAAYIrY74aAiCQKWckQGU80BKkRgkuE1eWpS-bQy9gifhnqyO2tnC9IJ3Vos-o-lpTTaifwNt-4AaBwdOis36FLBDbYaSBVxJ-XmNBiRGnMCGCG7u1wv4_eQ-21FoAh18zTE7WhUP13eJD6JsvK77tvJHz__nx3_xspEq_wBQTHKr</recordid><startdate>20100615</startdate><enddate>20100615</enddate><creator>Bianco, S</creator><creator>Musetti, C</creator><creator>Waldeck, A</creator><creator>Sparapani, S</creator><creator>Seitz, J. D</creator><creator>Krapcho, A. P</creator><creator>Palumbo, M</creator><creator>Sissi, C</creator><scope/></search><sort><creationdate>20100615</creationdate><title>Bis-phenanthroline derivatives as suitable scaffolds for effective G-quadruplex recognitionElectronic supplementary information (ESI) available: Additional data. See DOI: 10.1039/c0dt00038h</title><author>Bianco, S ; Musetti, C ; Waldeck, A ; Sparapani, S ; Seitz, J. D ; Krapcho, A. P ; Palumbo, M ; Sissi, C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-rsc_primary_c0dt00038h3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bianco, S</creatorcontrib><creatorcontrib>Musetti, C</creatorcontrib><creatorcontrib>Waldeck, A</creatorcontrib><creatorcontrib>Sparapani, S</creatorcontrib><creatorcontrib>Seitz, J. D</creatorcontrib><creatorcontrib>Krapcho, A. P</creatorcontrib><creatorcontrib>Palumbo, M</creatorcontrib><creatorcontrib>Sissi, C</creatorcontrib></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bianco, S</au><au>Musetti, C</au><au>Waldeck, A</au><au>Sparapani, S</au><au>Seitz, J. D</au><au>Krapcho, A. P</au><au>Palumbo, M</au><au>Sissi, C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bis-phenanthroline derivatives as suitable scaffolds for effective G-quadruplex recognitionElectronic supplementary information (ESI) available: Additional data. See DOI: 10.1039/c0dt00038h</atitle><date>2010-06-15</date><risdate>2010</risdate><volume>39</volume><issue>25</issue><spage>5833</spage><epage>5841</epage><pages>5833-5841</pages><issn>1477-9226</issn><eissn>1477-9234</eissn><abstract>Selective recognition of DNA folding is central to multiple biological and pharmacological applications aimed at precise targeting of distinct genomic regions. Here, we focused on the recognition of physiologically relevant G-quadruplex (G-4) structures by bis-phenanthroline (bis-Phen) ligands containing two Phen moieties covalently linked through an amine or thioether bond. The transition metal ions Mn 2+ , Ni 2+ , Cu 2+ , and the biologically relevant Mg 2+ and Zn 2+ efficiently form 1 : 1 bis-Phen complexes characterised by a large planar structure fit to successfully recognise G-quartet arrangements. Interestingly, metal ion complexation dramatically affects ligand-stabilising effects on G-quadruplex, the melting temperature of the folded structure being increased up to 30 °C at ligand concentrations as low as 1 μM in the presence of Ni 2+ and Cu 2+ . In addition, the test complexes were able to induce G-4 formation from essentially unfolded G-rich sequences even in the absence of K + ions as shown by gel shift and circular dichroism experiments. In line with their G-4 stabilising properties bis-Phen complexes are effective inhibitors of telomerase activity, Ni( ii ) complexes being effective in the sub-micromolar range. This is combined with lack of unselective DNA-damaging activity and short-term cellular toxicity, which makes the novel compounds (above all their Ni( ii ) complexes) interesting antiproliferative drug leads. Transition metal ions Mn 2+ , Ni 2+ , Cu 2+ , and the biologically relevant Mg 2+ and Zn 2+ efficiently form 1 : 1 bis-Phen complexes characterised by a large planar structure fit to successfully recognise G-quartet arrangements.</abstract><doi>10.1039/c0dt00038h</doi><tpages>9</tpages></addata></record>
fulltext fulltext
identifier ISSN: 1477-9226
ispartof
issn 1477-9226
1477-9234
language eng
recordid cdi_rsc_primary_c0dt00038h
source Royal Society Of Chemistry Journals; Alma/SFX Local Collection
title Bis-phenanthroline derivatives as suitable scaffolds for effective G-quadruplex recognitionElectronic supplementary information (ESI) available: Additional data. See DOI: 10.1039/c0dt00038h
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T20%3A18%3A55IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-rsc&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Bis-phenanthroline%20derivatives%20as%20suitable%20scaffolds%20for%20effective%20G-quadruplex%20recognitionElectronic%20supplementary%20information%20(ESI)%20available:%20Additional%20data.%20See%20DOI:%2010.1039/c0dt00038h&rft.au=Bianco,%20S&rft.date=2010-06-15&rft.volume=39&rft.issue=25&rft.spage=5833&rft.epage=5841&rft.pages=5833-5841&rft.issn=1477-9226&rft.eissn=1477-9234&rft_id=info:doi/10.1039/c0dt00038h&rft_dat=%3Crsc%3Ec0dt00038h%3C/rsc%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rfr_iscdi=true