324045-30-9Relevant academic research and scientific papers
FRET-BASED ZINC(II) ION INDICATOR
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Paragraph 0071-0073, (2013/03/28)
The present invention is directed to an indicator for targeting zinc(II) ions in a composition, e.g., a biological sample such as for targeting mitochondrial zinc (II) ions. The present invention is directed to a method for preparing an indicator that targets mitochondrial zinc(II), and a method of measuring the concentration of mitochondrial zinc(II) ions.
Structure-based design and evaluation of naphthalene diimide G-quadruplex ligands as telomere targeting agents in pancreatic cancer cells
Micco, Marialuisa,Collie, Gavin W.,Dale, Aaron G.,Ohnmacht, Stephan A.,Pazitna, Ingrida,Gunaratnam, Mekala,Reszka, Anthony P.,Neidle, Stephen
supporting information, p. 2959 - 2974 (2013/06/05)
Tetra-substituted naphthalene diimide (ND) derivatives with positively charged termini are potent stabilizers of human telomeric and gene promoter DNA quadruplexes and inhibit the growth of human cancer cells in vitro and in vivo. The present study reports the enhancement of the pharmacological properties of earlier ND compounds using structure-based design. Crystal structures of three complexes with human telomeric intramolecular quadruplexes demonstrate that two of the four strongly basic N-methyl-piperazine groups can be replaced by less basic morpholine groups with no loss of intermolecular interactions in the grooves of the quadruplex. The new compounds retain high affinity to human telomeric quadruplex DNA but are 10-fold more potent against the MIA PaCa-2 pancreatic cancer cell line, with IC50 values of ～10 nM. The lead compound induces cellular senescence but does not inhibit telomerase activity at the nanomolar dosage levels required for inhibition of cellular proliferation. Gene array qPCR analysis of MIA PaCa-2 cells treated with the lead compound revealed significant dose-dependent modulation of a distinct subset of genes, including strong induction of DNA damage responsive genes CDKN1A, DDIT3, GADD45A/G, and PPM1D, and repression of genes involved in telomere maintenance, including hPOT1 and PARP1.
The influence of positional isomerism on G-quadruplex binding and anti-proliferative activity of tetra-substituted naphthalene diimide compounds
Mpima, Sheila,Ohnmacht, Stephan A.,Barletta, Maria,Husby, Jarmila,Pett, Luke C.,Gunaratnam, Mekala,Hilton, Stephen T.,Neidle, Stephen
, p. 6162 - 6170 (2013/10/21)
The synthesis together with biophysical and biological evaluation of a series of tetra-substituted naphthalene diimide (ND) compounds, are presented. These compounds are positional isomers of a recently-described series of quadruplex-binding ND derivatives, in which the two N-methyl-piperidine-alkyl side-chains have now been interchanged with the positions of side-chains bearing a range of end-groups. Molecular dynamics simulations of a pair of positional isomers are in accord with the quadruplex stabilization and biological data for these compounds. Analysis of structure-activity data indicates that for compounds where the side-chains are not of equivalent length then the positional isomers described here tend to have improved cell proliferation potency and in some instances, superior quadruplex stabilization ability.
A FRET-based indicator for imaging mitochondrial zinc ions
Sreenath, Kesavapillai,Allen, John R.,Davidson, Michael W.,Zhu, Lei
supporting information; experimental part, p. 11730 - 11732 (2011/12/15)
A strategy based on fluorescence resonance energy transfer (FRET) to transform a red-emitting fluorophore into a ratiometric indicator for mitochondrial ZnII is demonstrated.
