File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Stabilization of G-quadruplex DNA with platinum(II) Schiff base complexes: Luminescent probe and down-regulation of c-myc oncogene expression

TitleStabilization of G-quadruplex DNA with platinum(II) Schiff base complexes: Luminescent probe and down-regulation of c-myc oncogene expression
Authors
KeywordsG-quadruplex DNA
Luminescent probes
Onogenes
Platinum
Schiff bases
Issue Date2009
PublisherWiley - V C H Verlag GmbH & Co KGaA. The Journal's web site is located at http://www.wiley-vch.de/home/chemistry
Citation
Chemistry - A European Journal, 2009, v. 15 n. 47, p. 13008-13021 How to Cite?
AbstractThe interactions of a series of platinum(II) Schiff base complexes with c-myc G-quadruplex DNA were studied. Complex [PtL1a] (1a; H 2L1a= N,N'-bis(salicylidene)-4,5-methoxy-1,2- phenylenediamine) can moderately inhibit c-myc gene promoter activity in a cell-free system through stabilizing the G-quadruplex structure and can inhibit c-myc oncogene expression in cultured cells. The interaction between 1a and G-quadruplex DNA has been examined by 1H NMR spectroscopy. By using computer-aided structure-based drug design for hit-to-lead optimization, an in silico G-quadruplex DNA model has been constructed for docking-based virtual screening to develop new platinum(II) Schiff base complexes with improved inhibitory activities. Complex [PtL3] (3; H2L 3=N,N'-bis{4-[1-(2-propylpiperidine)oxy]salicylidene}-4,5-methoxy-1, 2-phenylenediamine) has been identified with a top score in the virtual screening. This complex was subsequently prepared and experimentally tested in vitro for its ability to stabilize or induce the formation of the c-myc G-quadruplex. The inhibitory activity of 3 (IC50 = 4.4 μm) is tenfold more than that of 1a. The interaction between 1a or 3 with c-myc G-quadruplex DNA has been examined by absorption titration, emission titration, molecular modeling, and NMR titration experiments, thus revealing that both 1a and 3 bind c-myc G-quadruplex DNA through an external end-stacking mode at the 3' terminal face of the G-quadruplex. Such binding of G-quadruplex DNA with 3 is accompanied by up to an eightfold increase in the intensity of photoluminescence at λmax = 652 nm. Complex 3 also effectively down-regulated the expression of c-myc in human hepatocarcinoma cells. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Persistent Identifierhttp://hdl.handle.net/10722/69206
ISSN
2015 Impact Factor: 5.771
2015 SCImago Journal Rankings: 2.323
ISI Accession Number ID
Funding AgencyGrant Number
Area of Excellence Scheme established under the University Grants Committee (HKSAR, China)AoE/P-10/01
University of Hong Kong
Chinese Academy of Sciences-Croucher Foundation
Funding Information:

This work was supported by the Area of Excellence Scheme established under the University Grants Committee (HKSAR, China (AoE/P-10/01), the University of Hong Kong (University Development Fund), and The Chinese Academy of Sciences-Croucher Foundation Funding Scheme For Joint Laboratories.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorWu, Pen_HK
dc.contributor.authorMa, DLen_HK
dc.contributor.authorLeung, CHen_HK
dc.contributor.authorYan, SCen_HK
dc.contributor.authorZhu, Nen_HK
dc.contributor.authorAbagyan, Ren_HK
dc.contributor.authorChe, CMen_HK
dc.date.accessioned2010-09-06T06:11:32Z-
dc.date.available2010-09-06T06:11:32Z-
dc.date.issued2009en_HK
dc.identifier.citationChemistry - A European Journal, 2009, v. 15 n. 47, p. 13008-13021en_HK
dc.identifier.issn0947-6539en_HK
dc.identifier.urihttp://hdl.handle.net/10722/69206-
dc.description.abstractThe interactions of a series of platinum(II) Schiff base complexes with c-myc G-quadruplex DNA were studied. Complex [PtL1a] (1a; H 2L1a= N,N'-bis(salicylidene)-4,5-methoxy-1,2- phenylenediamine) can moderately inhibit c-myc gene promoter activity in a cell-free system through stabilizing the G-quadruplex structure and can inhibit c-myc oncogene expression in cultured cells. The interaction between 1a and G-quadruplex DNA has been examined by 1H NMR spectroscopy. By using computer-aided structure-based drug design for hit-to-lead optimization, an in silico G-quadruplex DNA model has been constructed for docking-based virtual screening to develop new platinum(II) Schiff base complexes with improved inhibitory activities. Complex [PtL3] (3; H2L 3=N,N'-bis{4-[1-(2-propylpiperidine)oxy]salicylidene}-4,5-methoxy-1, 2-phenylenediamine) has been identified with a top score in the virtual screening. This complex was subsequently prepared and experimentally tested in vitro for its ability to stabilize or induce the formation of the c-myc G-quadruplex. The inhibitory activity of 3 (IC50 = 4.4 μm) is tenfold more than that of 1a. The interaction between 1a or 3 with c-myc G-quadruplex DNA has been examined by absorption titration, emission titration, molecular modeling, and NMR titration experiments, thus revealing that both 1a and 3 bind c-myc G-quadruplex DNA through an external end-stacking mode at the 3' terminal face of the G-quadruplex. Such binding of G-quadruplex DNA with 3 is accompanied by up to an eightfold increase in the intensity of photoluminescence at λmax = 652 nm. Complex 3 also effectively down-regulated the expression of c-myc in human hepatocarcinoma cells. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.en_HK
dc.languageengen_HK
dc.publisherWiley - V C H Verlag GmbH & Co KGaA. The Journal's web site is located at http://www.wiley-vch.de/home/chemistryen_HK
dc.relation.ispartofChemistry - A European Journalen_HK
dc.subjectG-quadruplex DNAen_HK
dc.subjectLuminescent probesen_HK
dc.subjectOnogenesen_HK
dc.subjectPlatinumen_HK
dc.subjectSchiff basesen_HK
dc.subject.meshG-Quadruplexes - drug effects-
dc.subject.meshOrganoplatinum Compounds - chemistry - metabolism - pharmacology-
dc.subject.meshPlatinum - chemistry-
dc.subject.meshProto-Oncogene Proteins c-myc - chemistry - genetics - metabolism-
dc.subject.meshSchiff Bases - chemistry - metabolism - pharmacology-
dc.titleStabilization of G-quadruplex DNA with platinum(II) Schiff base complexes: Luminescent probe and down-regulation of c-myc oncogene expressionen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0947-6539&volume=15&issue=47&spage=13008&epage=13021&date=2009&atitle=Stabilization+of+G-quadruplex+DNA+with+platinum(II)+Schiff+base+complexes:+luminescent+probe+and+down-regulation+of+c-myc+oncogene+expressionen_HK
dc.identifier.emailMa, DL: edmondma@hku.hken_HK
dc.identifier.emailLeung, CH: duncanl@hkucc.hku.hken_HK
dc.identifier.emailZhu, N: nzhu@hkucc.hku.hken_HK
dc.identifier.emailChe, CM: cmche@hku.hken_HK
dc.identifier.authorityMa, DL=rp00760en_HK
dc.identifier.authorityLeung, CH=rp00730en_HK
dc.identifier.authorityZhu, N=rp00845en_HK
dc.identifier.authorityChe, CM=rp00670en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/chem.200901943en_HK
dc.identifier.pmid19876976-
dc.identifier.scopuseid_2-s2.0-73349096880en_HK
dc.identifier.hkuros169752en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-73349096880&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume15en_HK
dc.identifier.issue47en_HK
dc.identifier.spage13008en_HK
dc.identifier.epage13021en_HK
dc.identifier.isiWOS:000273697100015-
dc.publisher.placeGermanyen_HK
dc.relation.projectInstitute of molecular technology for drug discovery and synthesis-
dc.identifier.scopusauthoridWu, P=7403119736en_HK
dc.identifier.scopusauthoridMa, DL=7402075538en_HK
dc.identifier.scopusauthoridLeung, CH=7402612570en_HK
dc.identifier.scopusauthoridYan, SC=7401744858en_HK
dc.identifier.scopusauthoridZhu, N=7201449530en_HK
dc.identifier.scopusauthoridAbagyan, R=7006710879en_HK
dc.identifier.scopusauthoridChe, CM=7102442791en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats