Selective G-quadruplex ligands: The significant role of side chain charge density in a series of perylene derivatives

Micheli, Emanuela; Lombardo, Caterina Maria; D’Ambrosio, Danilo; Franceschin, Marco; Neidle, Stephen; Savino, M.

doi:10.1016/j.bmcl.2009.03.106

Cited by 24 publications

(30 citation statements)

References 18 publications

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“…[5,9] Even there studies were often performed as parallel experiments to those with G-quadruplexes. [10] Investigations of PBI-DNA conjugates have shown that stacked PBI molecules within the DNA scaffold give specific induced circular dichroism (ICD) profiles, which are strongly dependento nt he freedom of adjustment of PBI molecules in the DNA. [11] This finding suggeststhat PBI dyes can be used as sensitive probes for the chiral environmento fp olynucleotides and as non-covalently interacting sensors for various DNA and RNA structures.…”

Section: Introductionmentioning

confidence: 99%

Sensing of Double‐Stranded DNA/RNA Secondary Structures by Water Soluble Homochiral Perylene Bisimide Dyes

Gershberg

Stojković

Škugor

et al. 2015

Chemistry A European J

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A broad series of homochiral perylene bisimide (PBI) dyes were synthesized that are appended with amino acids and cationic side chains at the imide positions. Self-assembly behavior of these ionic PBIs has been studied in aqueous media by UV/Vis spectroscopy, revealing formation of excitonically coupled H-type aggregates. The interactions of these ionic PBIs with different ds-DNA and ds-RNA have been explored by thermal denaturation, fluorimetric titration and circular dichroism (CD) experiments. These PBIs strongly stabilized ds-DNA/RNA against thermal denaturation as revealed by high melting temperatures of the formed PBI/polynucleotide complexes. Fluorimetric titrations showed that these PBIs bind to ds-DNA/RNA with high binding constants depending on the number of the positive charges in the side chains. Thus, spermine-containing PBIs with six positive charges each showed higher binding constants (logKs =9.2-9.8) than their dioxa analogues (logKs =6.5-7.9) having two positive charges each. Induced circular dichroism (ICD) of PBI assemblies created within DNA/RNA grooves was observed. These ICD profiles are strongly dependent on the steric demand of the chiral substituents of the amino acid units and the secondary structure of the DNA or RNA. The observed ICD effects can be explained by non-covalent binding of excitonically coupled PBI dimer aggregates into the minor groove of DNA and major groove of RNA which is further supported by molecular modeling studies.

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Section: Introductionmentioning

confidence: 99%

Sensing of Double‐Stranded DNA/RNA Secondary Structures by Water Soluble Homochiral Perylene Bisimide Dyes

Gershberg

Stojković

Škugor

et al. 2015

Chemistry A European J

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“…Unlike CD spectra recorded for compound 7 in complex with the G-quadruplex, the spectra recorded for ds-22 in the ligand region show only a weak ICD signal (Supporting Information). The weak negative ICD band at ~580 nm observed for the 2:1 complex can be attributed to the formation of exciton-coupled stacked dimers of compound 7 in the DNA minor groove, which is reminiscent of the non-intercalative binding mode proposed for perylenediimide derivatives 30 . Incubation at elevated temperature had no effect on the CD spectrum.…”

Section: Resultsmentioning

confidence: 81%

“…Binding of compound 7 to this form of G-quadruplex is supported by the appearance of an induced CD (ICD) signal in the ligand region consisting of a negative band at 502 nm and a positive band at 559 nm, both increasing linearly with the addition of ligand (Figure 2B). The distinct bisignate nature of this signal indicates exciton coupling between multiple bound perylene chromophores 30,35 . Previous NMR studies have demonstrated that the perylenediimide agent PIPER forms a 1:1 complex with the parallel G-quadruplex, in which the ligand stacks with the G-tetrad formed at the 5´-GT step 17 .…”

Section: Resultsmentioning

confidence: 97%

Interactions of a Platinum-Modified Perylene Derivative with the Human Telomeric G-Quadruplex

et al. 2011

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The interactions of a newly synthesized platinum-modified perylene derivative, compound 7 ([{Pt(dien)}2(μ-4-S,S')](NO3)4 (dien = diethylenetriamine, 4 = N,N'-bis(1-(2-aminoethyl)-1,3-dimethylthiourea)-3,4,9,10-perylenetetracarboxylic acid diimide), with the human telomeric repeat were studied using various model oligo(deoxy)ribonucleotides to mimic the polymorphic nature of the telomeric G-quadruplex. UV/visible spectroscopy, CD spectropolarimetry, electrospray mass spectrometry (ES-MS), and isothermal titration calorimetry (ITC) were used to demonstrate that compound 7 selectively recognizes the antiparallel form of the unimolecular telomeric G-quadruplex formed by the sequence d(TTAGGG)4 (dG-24), to which it binds with a 2:1 stoichiometry and nanomolar affinity. Compared with telomeric DNA, the first binding event of compound 7 in titrations with the RNA quadruplex formed by r(UUAGGG)4 (rG-24) is an order of magnitude weaker. Compound 7 does not induce the antiparallel G-quadruplex RNA, which invariably exists in a parallel form and dimerizes in solution. Based on the cumulative experimental data, two distinct mechanisms are proposed for the recognition of G-quadruplex DNA and RNA by compound 7. Potential biomedical and biochemical applications of the platinum–perylene technology are discussed.

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“…1 Numerous studies using various active ingredients were performed to inhibit TA. Beside the G-quadruplex ligands, [10][11][12] small synthetic and nucleic acids based telomerase inhibitors, there is a multiplicity of compounds that can cause a decrease in TA. 1 Differentiating agents like all-trans retinoic acids, adriamycin and doxorubicin reduced TA and hTERT mRNA expression.…”

Section: Discussionmentioning

confidence: 99%

“…1 Among the latter, several compounds have been reported include rubromycins, 4 alterperylenol, 5 epigallocatechin gallate, 6 anthraquinone derivatives, 7-9 G-quadruplex ligands. [10][11][12] In our previous studies, we found that loss of telomerase activity can be potentially favorable prognostic marker in lung carcinomas. [13][14][15][16] We are currently undertaking the therapeutic assessment of medicinal mushroom Antrodia camphorata.…”

Section: Introductionmentioning

confidence: 99%

Identification of small molecule inhibitors of telomerase activity through transcriptional regulation of hTERT and calcium induction pathway in human lung adenocarcinoma A549 cells

Rao

Kao

et al. 2010

Bioorganic & Medicinal Chemistry

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Selective G-quadruplex ligands: The significant role of side chain charge density in a series of perylene derivatives

Cited by 24 publications

References 18 publications

Sensing of Double‐Stranded DNA/RNA Secondary Structures by Water Soluble Homochiral Perylene Bisimide Dyes

Sensing of Double‐Stranded DNA/RNA Secondary Structures by Water Soluble Homochiral Perylene Bisimide Dyes

Interactions of a Platinum-Modified Perylene Derivative with the Human Telomeric G-Quadruplex

Identification of small molecule inhibitors of telomerase activity through transcriptional regulation of hTERT and calcium induction pathway in human lung adenocarcinoma A549 cells

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