About: Regulating Bioactivity of Cu2+ Bis-1,10-phenanthroline Artificial Metallonucleases with Sterically Functionalized Pendant Carboxylates     Goto   Sponge   NotDistinct   Permalink

An Entity of Type : http://linked.opendata.cz/ontology/domain/vavai/Vysledek, within Data Space : linked.opendata.cz associated with source document(s)

AttributesValues
rdf:type
rdfs:seeAlso
Description
  • The synthetic chemical nuclease, [Cu(1,10-phenanthroline)(2)](2+), has stimulated research within metallonuclease development and in the area of cytotoxic metallodrug design. Our analysis reveals, however, that this agent is %22promiscuous%22 as it binds both dsDNA and protein biomolecules, without specificity, and induces general toxicity to a diversity of cell lineages. Here, we describe the synthesis and characterization of small-molecule metallonucleases containing the redox-active cation, [Cu(RCOO)(1,10-phen)(2)](+), where 1,10-phen = 1,10-phenanthroline and R = -H, -CH3, -C2H5, -CH(CH3)(2), and -C(CH3)(3). The presence of coordinated carboxylate groups in the complex cation functions to enhance dsDNA recognition, reduce serum albumin binding, and offer control of toxicity toward human cancer cells, Gram positive and negative bacteria, and fungal pathogens. The induction of genomic dsDNA breaks (DSBs) were identified in ovarian adenocarcinoma cells using immunodetection of gamma-H2AX. Formate, acetate, and pivalate functionalized complexes induced DSBs in a higher percentage of cells compared with [Cu(1,10-phen)(2)](2+), which supports the importance of inner-sphere modification toward enhancing targeted biological application.
  • The synthetic chemical nuclease, [Cu(1,10-phenanthroline)(2)](2+), has stimulated research within metallonuclease development and in the area of cytotoxic metallodrug design. Our analysis reveals, however, that this agent is %22promiscuous%22 as it binds both dsDNA and protein biomolecules, without specificity, and induces general toxicity to a diversity of cell lineages. Here, we describe the synthesis and characterization of small-molecule metallonucleases containing the redox-active cation, [Cu(RCOO)(1,10-phen)(2)](+), where 1,10-phen = 1,10-phenanthroline and R = -H, -CH3, -C2H5, -CH(CH3)(2), and -C(CH3)(3). The presence of coordinated carboxylate groups in the complex cation functions to enhance dsDNA recognition, reduce serum albumin binding, and offer control of toxicity toward human cancer cells, Gram positive and negative bacteria, and fungal pathogens. The induction of genomic dsDNA breaks (DSBs) were identified in ovarian adenocarcinoma cells using immunodetection of gamma-H2AX. Formate, acetate, and pivalate functionalized complexes induced DSBs in a higher percentage of cells compared with [Cu(1,10-phen)(2)](2+), which supports the importance of inner-sphere modification toward enhancing targeted biological application. (en)
Title
  • Regulating Bioactivity of Cu2+ Bis-1,10-phenanthroline Artificial Metallonucleases with Sterically Functionalized Pendant Carboxylates
  • Regulating Bioactivity of Cu2+ Bis-1,10-phenanthroline Artificial Metallonucleases with Sterically Functionalized Pendant Carboxylates (en)
skos:prefLabel
  • Regulating Bioactivity of Cu2+ Bis-1,10-phenanthroline Artificial Metallonucleases with Sterically Functionalized Pendant Carboxylates
  • Regulating Bioactivity of Cu2+ Bis-1,10-phenanthroline Artificial Metallonucleases with Sterically Functionalized Pendant Carboxylates (en)
skos:notation
  • RIV/00216208:11160/13:10196566!RIV14-MSM-11160___
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • I
http://linked.open...iv/cisloPeriodika
  • 21
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
http://linked.open.../riv/druhVysledku
http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 102066
http://linked.open...ai/riv/idVysledku
  • RIV/00216208:11160/13:10196566
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • 10-phenanthroline; 1; histone H2AX; strand breaks; anticancer activity; copper(II) complexes; DNA-binding; chemical nucleases; in-vitro; cancer-cell-lines; carbon-hydrogen bonds (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • US - Spojené státy americké
http://linked.open...ontrolniKodProRIV
  • [135543276866]
http://linked.open...i/riv/nazevZdroje
  • Journal of Medicinal Chemistry
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 56
http://linked.open...iv/tvurceVysledku
  • Pour, Milan
  • Gathergood, Nicholas
  • Barron, Niall
  • Colleran, John
  • Howe, Orla
  • Kellett, Andrew
  • McCann, Malachy
  • McKee, Vickie
  • Prisecaru, Andreea
  • Rochford, Garret
http://linked.open...ain/vavai/riv/wos
  • 000327111100030
issn
  • 0022-2623
number of pages
http://bibframe.org/vocab/doi
  • 10.1021/jm401465m
http://localhost/t...ganizacniJednotka
  • 11160
Faceted Search & Find service v1.16.118 as of Jun 21 2024


Alternative Linked Data Documents: ODE     Content Formats:   [cxml] [csv]     RDF   [text] [turtle] [ld+json] [rdf+json] [rdf+xml]     ODATA   [atom+xml] [odata+json]     Microdata   [microdata+json] [html]    About   
This material is Open Knowledge   W3C Semantic Web Technology [RDF Data] Valid XHTML + RDFa
OpenLink Virtuoso version 07.20.3240 as of Jun 21 2024, on Linux (x86_64-pc-linux-gnu), Single-Server Edition (126 GB total memory, 48 GB memory in use)
Data on this page belongs to its respective rights holders.
Virtuoso Faceted Browser Copyright © 2009-2024 OpenLink Software