New triple-helix DNA stabilizing agents

Strękowski, Lucjan; Hojjat, Maryam; Wolińska, Ewa; Parker, Alesia N.; Paliakov, Ekaterina; Górecki, Tadeusz; Tanious, Farial A.; Wilson, W. David

doi:10.1016/j.bmcl.2004.12.019

Cited by 22 publications

(8 citation statements)

References 12 publications

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“…We also demonstrated that the dicationic hetarenes 12 and 13 stabilize the poly(dA)-[poly(dT)] 2 triplex upon association, 41 as indicated by ∆T m 3→2 values that are still among the largest observed under such conditions. 42,43 In addition, most of these ligands show an excellent triplex-versus-duplex selectivity at low ligand-DNA ratios (Table 2). Hence, the duplex DNA is only nominally stabilized on addition of the ligands as clearly shown by a comparison of the ∆T m 3→2 and ∆T m 2→1 values.…”

Section: Account Syn Lettmentioning

confidence: 99%

Playing Around with the Size and Shape of Quinolizinium Derivatives: Versatile Ligands for Duplex, Triplex, Quadruplex and Abasic Site-Containing DNA

Granzhan

Ihmels

2016

Synlett

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The association of heteroaromatic ligands with DNA is an important and biologically relevant process, because it may have a strong influence on the function of the nucleic acid. As a result, efficient and selective DNA-targeting ligands are considered as promising lead structures for drugs. In this context, we established the quinolizinium ion as a versatile building block for the design of DNA-binding ligands, with the long-term goal to evaluate and understand the structural parameters that govern the association of cationic hetarenes with DNA. In this account we demonstrate that annelated quinolizinium derivatives are easily available and that their structure and substitution pattern are highly variable. Most notably, the availability of several derivatives with different size and shape enables the assessment of structure-property relationships regarding their DNA-binding properties. It is shown with exemplary case studies that the systematic variation of the ligand structure, along with analysis of the binding parameters, can be employed to analyze the structural requirements of a ligand to bind to different DNA forms, such as triplex, quadruplex and abasic site-containing DNA. Conclusion Key words DNA binders, heterocycles, intercalators, polycyclic hetarenes, quinolizinium surprising that nitrogen-containing polycyclic hetarenes also have a high propensity to bind to DNA. In fact, hetarenes such as acridine (1a), acridine orange (1b) or ethidium (2) are the paradigm of a DNA intercalator, 6 i.e., a ligand

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Section: Account Syn Lettmentioning

confidence: 99%

Playing Around with the Size and Shape of Quinolizinium Derivatives: Versatile Ligands for Duplex, Triplex, Quadruplex and Abasic Site-Containing DNA

Granzhan

Ihmels

2016

Synlett

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“…Besides, 4,7-phenathroline derivatives were found to exhibit staining properties to HeLa cells and can be used as fluorophores which can bind with proteins 23 . Other derivatives were reported as high affinity triple-helix DNA stabilizing agents 24 .…”

Section: Introductionmentioning

confidence: 99%

Synthesis, structure, antimycobacterial and anticancer evaluation of new pyrrolo-phenanthroline derivatives

Matarneh

Mangalagiu

Shova³

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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A study concerning design, synthesis, structure and in vitro antimycobacterial and anticancer evaluation of new fused derivatives with pyrrolo[2,1-c] [4,7]phenanthroline skeleton is described. The strategy adopted for synthesis involves a [3 + 2] dipolar cycloaddition of several in situ generated 4,7-phenanthrolin-4-ium ylides to different substituted alkynes and alkenes. Stereo-and regiochemistry of cycloaddition reactions were discussed. The structure of the new compounds was proven unambiguously, single-crystal X-ray diffraction studies including. The antimycobacterial and anticancer activity of a selection of new synthesized compounds was evaluated against Mycobacterium tuberculosis H37Rv under aerobic conditions and 60 human tumour cell line panel, respectively. Five of the tested compounds possess a moderate antimycobacterial activity, while two of the compounds have a significant antitumor activity against renal cancer and breast cancer.

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“…18, 19, 19-21 Intercalators usually stabilize to a greater extent triple helices containing TAT triplets, whereas minor groove binders usually destabilize triplexes. 22 At the beginning of this millennium, when we began our work on recognition of nucleic acids, one surprising fact stared at us: While there were a number of intercalators that stabilized DNA duplex and triplex structures (selectively and non-selectively), there were no examples of groove-binding ligands that selectively recognized the triple helices (spermine, 23 with its flexible amines as the possible weak exception).…”

Section: Introductionmentioning

confidence: 99%

New Approaches Toward Recognition of Nucleic Acid Triple Helices

Arya¹

2010

Acc. Chem. Res.

151

116

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We show that groove recognition of nucleic acid triple helices can be achieved with aminosugars. Among these aminosugars, neomycin is the most effective aminoglycoside (groove binder) for stabilizing a DNA triple helix. It stabilizes both the T·A·T triplex and mixed-base DNA triplexes better than known DNA minor groove binders (which usually destabilize the triplex) and polyamines. Neomycin selectively stabilizes the triplex (T·A·T and mixed base) without any effect on the DNA duplex. The selectivity of neomycin likely originates from its potential and shape complementarity to the triplex Watson–Hoogsteen groove, making it the first molecule that selectively recognizes a triplex groove over a duplex groove. The groove recognition of aminoglycosides is not limited to DNA triplexes, but also extends to RNA and hybrid triple helical structures. Intercalator–neomycin conjugates are shown to simultaneously probe the base stacking and groove surface in the DNA triplex. Calorimetric and spectrosocopic studies allow the quantification of the effect of surface area of the intercalating moiety on binding to the triplex. These studies outline a novel approach to the recognition of DNA triplexes that incorporates the use of non-competing binding sites. These principles of dual recognition should be applicable to the design of ligands that can bind any given nucleic acid target with nanomolar affinities and with high selectivity.

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New triple-helix DNA stabilizing agents

Cited by 22 publications

References 12 publications

Playing Around with the Size and Shape of Quinolizinium Derivatives: Versatile Ligands for Duplex, Triplex, Quadruplex and Abasic Site-Containing DNA

Playing Around with the Size and Shape of Quinolizinium Derivatives: Versatile Ligands for Duplex, Triplex, Quadruplex and Abasic Site-Containing DNA

Synthesis, structure, antimycobacterial and anticancer evaluation of new pyrrolo-phenanthroline derivatives

New Approaches Toward Recognition of Nucleic Acid Triple Helices

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New triple-helix DNA stabilizing agents

Cited by 22 publications

References 12 publications

Playing Around with the Size and Shape of Quinolizinium ­Derivatives: Versatile Ligands for Duplex, Triplex, Quadruplex and Abasic Site-Containing DNA

Playing Around with the Size and Shape of Quinolizinium ­Derivatives: Versatile Ligands for Duplex, Triplex, Quadruplex and Abasic Site-Containing DNA

Synthesis, structure, antimycobacterial and anticancer evaluation of new pyrrolo-phenanthroline derivatives

New Approaches Toward Recognition of Nucleic Acid Triple Helices

Contact Info

Product

Resources

About

Playing Around with the Size and Shape of Quinolizinium Derivatives: Versatile Ligands for Duplex, Triplex, Quadruplex and Abasic Site-Containing DNA

Playing Around with the Size and Shape of Quinolizinium Derivatives: Versatile Ligands for Duplex, Triplex, Quadruplex and Abasic Site-Containing DNA