Controlled Pore Glass-based oligonucleotide affinity support: towards High Throughput Screening methods for the identification of conformation-selective G-quadruplex ligands

Platella, Chiara; Musumeci, Domenica; Arciello, Angela; Doria, Filippo; Freccero, Mauro; Randazzo, Antonio; Amato, Jussara; Pagano, Bruno; Montesarchio, Daniela

doi:10.1016/j.aca.2018.04.071

Cited by 24 publications

(57 citation statements)

References 37 publications

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“…All the analyzed ligands exhibited a good affinity for tel26 and cmyc G4s immobilized on the solid supports, with the monomeric NDIs showing, in general, a higher affinity than the dimeric compounds (Table 1 and Supplementary Figures S1-S3). Moreover, the tested NDIs proved to be all effective G4 ligands, also in comparison with known G4 binders [26,27]. Among the investigated compounds, NDI-9 and NDI-10 showed the lowest affinity for the G4s.…”

Section: Preliminary Ndi Screening By the G4-cpg Assaymentioning

confidence: 96%

“…All the new molecular entities were prepared according to the synthetic protocols outlined in Figures 3 and 4. We used a well-established method for the preparation of the mixture of mono-(NDI-13) and dibromo-substituted (NDI-14) N,N'-bis((dimethylamino)propylamino) NDIs, directly This library of brand-new NDIs was then analyzed, to identify G4-selective ligands, using G4-functionalized Controlled Pore Glass solid supports in an affinity chromatography-based screening (G4-CPG assay) recently developed by some of us [26][27][28]. Next, the ligands featuring good affinity for the selected G4s, coupled with significant G4 vs. duplex DNA discrimination ability, were tested in their biological activity.…”

Section: Synthesis Of the Functionalized Monomeric And Dimeric Naphthmentioning

confidence: 99%

“…The affinity chromatography-based G4-CPG assay, recently described by some of us [26][27][28]32,33], consists in incubating putative G4 ligands solutions with Controlled Pore Glass (CPG) solid supports functionalized with different secondary structure-forming oligonucleotides. In this screening, defined volumes of a washing solution first, and then of releasing solutions, were flown Therefore, we performed a nucleophilic aromatic substitution on the dicarboxylic-acid-derivatized NDI-18, using one equivalent of pure NDI-3, or NDI-4 or NDI-16.…”

Section: Preliminary Ndi Screening By the G4-cpg Assaymentioning

confidence: 99%

“…The binding assays were performed by adopting previously reported protocols [26] (for details, see the Experimental Section). Ligand stock solutions were prepared by dissolving a weighed amount of the solid compound under investigation in H 2 O or pure DMSO, for monomeric and dimeric NDIs, respectively.…”

Section: Preliminary Ndi Screening By the G4-cpg Assaymentioning

confidence: 99%

“…This aspect justifies a systematic comparison of the selected oligoethyleneglycol vs. alkyl linkers [25]. This library of brand-new NDIs was then analyzed, to identify G4-selective ligands, using G4functionalized Controlled Pore Glass solid supports in an affinity chromatography-based screening (G4-CPG assay) recently developed by some of us [26][27][28]. Next, the ligands featuring good affinity for the selected G4s, coupled with significant G4 vs. duplex DNA discrimination ability, were tested in their biological activity.…”

Section: Introductionmentioning

confidence: 99%

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Trifunctionalized Naphthalene Diimides and Dimeric Analogues as G-Quadruplex-Targeting Anticancer Agents Selected by Affinity Chromatography

Platella

Pirota

Musumeci

et al. 2020

IJMS

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A focused library of newly designed monomeric and dimeric naphthalene diimides (NDIs) was analyzed in its ability to recognize specific G-quadruplex (G4) structures discriminating duplex DNA. The best G4 ligands—according to an affinity chromatography-based screening method named G4-CPG—were tested on human cancer and healthy cells, inducing DNA damage at telomeres, and in parallel, showing selective antiproliferative activity on HeLa cancer cells with IC50 values in the low nanomolar range. CD and fluorescence spectroscopy studies allowed detailed investigation of the interaction in solution with different G4 and duplex DNA models of the most promising NDI of the series, as determined by combining the biophysical and biological assays’ data.

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Section: Preliminary Ndi Screening By the G4-cpg Assaymentioning

confidence: 96%

Section: Synthesis Of the Functionalized Monomeric And Dimeric Naphthmentioning

confidence: 99%

Section: Preliminary Ndi Screening By the G4-cpg Assaymentioning

confidence: 99%

Section: Preliminary Ndi Screening By the G4-cpg Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Trifunctionalized Naphthalene Diimides and Dimeric Analogues as G-Quadruplex-Targeting Anticancer Agents Selected by Affinity Chromatography

Platella

Pirota

Musumeci

et al. 2020

IJMS

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Optimization of G‐Quadruplex Ligands through a SAR Study Combining Parallel Synthesis and Screening of Cationic Bis(acylhydrazones)

Reznichenko

Leclercq

Pinto

et al. 2022

Chemistry A European J

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General remarks: All commercially available chemicals were reagent grade and used without further purification. NMR spectra were measured with a Bruker Avance 300 spectrometer ( 1 H: 300 MHz, 13 C: 75 MHz) at 25 °C; chemical shifts are given in ppm (δ) values. Multiplicities of 13 C NMR signals were determined from DEPT-135 experiments. The melting points were determined in open-end capillaries with a digital melting point instrument (SMP30, Stuart).

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Affinity Chromatography‐Based Assays for the Screening of Potential Ligands Selective for G‐Quadruplex Structures

et al. 2022

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DNA G‐quadruplexes (G4s) are key structures for the development of targeted anticancer therapies. In this context, ligands selectively interacting with G4s can represent valuable anticancer drugs. Aiming at speeding up the identification of G4‐targeting synthetic or natural compounds, we developed an affinity chromatography‐based assay, named G‐quadruplex on Oligo Affinity Support (G4‐OAS), by synthesizing G4‐forming sequences on commercially available polystyrene OAS. Then, due to unspecific binding of several hydrophobic ligands on nude OAS, we moved to Controlled Pore Glass (CPG). We thus conceived an ad hoc functionalized, universal support on which both the on‐support elongation and deprotection of the G4‐forming oligonucleotides can be performed, along with the successive affinity chromatography‐based assay, renamed as G‐quadruplex on Controlled Pore Glass (G4‐CPG) assay. Here we describe these assays and their applications to the screening of several libraries of chemically different putative G4 ligands. Finally, ongoing studies and outlook of our G4‐CPG assay are reported.

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Controlled Pore Glass-based oligonucleotide affinity support: towards High Throughput Screening methods for the identification of conformation-selective G-quadruplex ligands

Cited by 24 publications

References 37 publications

Trifunctionalized Naphthalene Diimides and Dimeric Analogues as G-Quadruplex-Targeting Anticancer Agents Selected by Affinity Chromatography

Trifunctionalized Naphthalene Diimides and Dimeric Analogues as G-Quadruplex-Targeting Anticancer Agents Selected by Affinity Chromatography

Optimization of G‐Quadruplex Ligands through a SAR Study Combining Parallel Synthesis and Screening of Cationic Bis(acylhydrazones)

Affinity Chromatography‐Based Assays for the Screening of Potential Ligands Selective for G‐Quadruplex Structures

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