Recognition of thymine in DNA bulges by a Zn(ii) macrocyclic complex

Mundo, Imee Marie A. del; Fountain, Matthew A.; Morrow, Janet R.

doi:10.1039/c1cc12074c

Cited by 18 publications

(44 citation statements)

References 37 publications

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“…In particular, we chose the cyclen unit as a second coordinating ligand because: (a) cyclen does not coordinate with high affinity to platinum(II) and therefore it was possible to prepare mixed-metal complexes (11 and 12); (b) zinc(II)-cyclen complexes have been previously reported to have good affinity for phosphates [39][40][41][42] and hence we rationalised that this type of moiety would be able to interact with the phosphate backbone of DNA; furthermore, it is well established that zinc(II)-cyclen complexes have high affinity for thymine and therefore one could expect strong interactions with bases in the loops of DNA. [43][44][45][46][47] Indeed, the results obtained indicate that these bi-metallic complexes are excellent quadruplex DNA binders and the cyclen unit seems to provide them with high affinity over duplex DNA (even for complex 10 where the cyclen is metal-free). UV-Vis spectroscopic titrations were also used to probe the binding mode between the complexes and the different DNA structures.…”

Section: Biophysical Studies To Determine the Interactions Between Mementioning

confidence: 94%

Syntheses of polypyridyl metal complexes and studies of their interaction with quadruplex DNA

et al. 2015

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A series of mono- and bi-metallic metal complexes (with Cu(II), Pt(II) and Zn(II)) with substituted polypyridyl ligands have been prepared and their binding affinities towards quadruplex (c-Myc and human telomeric) and duplex DNA (ds26 and calf thymus) determined using fluorescent indicator displacement (FID) assays and UV/vis spectroscopic titrations. These studies have shown that the number of aromatic rings and number/position of cyclic amine substituents on the ligands, play an important role in defining the DNA binding abilities of the resulting metal complexes. We also show that bi-metallic complexes prepared using a novel terpyridine-cyclen ligand have higher affinity towards G-quadruplex DNA as compared to their mono-metallic counterparts. Cytotoxicity assays were carried out for all the new complexes against an osteosarcoma cancer cell line (U2OS) as well as a normal fibroblast cell line (GM05757). Several of these compounds displayed cytotoxicity similar to that of cisplatin.

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Section: Biophysical Studies To Determine the Interactions Between Mementioning

confidence: 94%

Syntheses of polypyridyl metal complexes and studies of their interaction with quadruplex DNA

et al. 2015

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“…As shown previously, the macrocycles bind tightly to the Zn(II) ion to give complexes which are >90% intact even at micromolar concentrations of Zn(II) and macrocycle at neutral pH. [28][29][30] The pendents have distinct ring structures as well as connections to the macrocycle through different types of linkers including a methylene (ML), sulfone (SL) or direct attachment (DL).…”

Section: Macrocyclic Complexesmentioning

confidence: 86%

“…For example, the interaction of Zn(II) complexes with unpaired thymines in non-canonical context including those in bulged DNA and quadruplex DNA has been reported. [28][29][30] Binding of a Zn(II) complex to thymine mismatches has also been studied. [31] Applications include of Zn(II) cyclen binding to thymine mismatches include enhanced specificity of DNA polymerase chain reactions, and more accurate analysis of single nucleotide polymorphisms.…”

Section: Introductionmentioning

confidence: 99%

“…[32][33][34] For recognition of such non-canonical DNA, the pendents may interact with the unpaired thymines as they do in simple oligonucleotides, or with other elements in the DNA structure. [29] Notably, there are restrictions on the size and structure of the pendent that optimize the selective binding of Zn(II) complexes to unpaired thymine versus duplex DNA. Zn(II) complexes with pendents containing two fused rings show increased binding for non-canonical thymine over duplex DNA.…”

Section: Introductionmentioning

confidence: 99%

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Zn(II) complexes that trigger a DNA conformational switch

Sander

Morrow

2016

Inorganica Chimica Acta

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Several Zn(II) complexes are shown to produce a DNA conformational switch that involves dissociation of a fully complementary duplex into two hairpins. Of the three different pendent groups studied, a Zn(II) complex with a planar pendent connected directly to the macrocycle is the most effective at promoting the conformational switch. DNA duplexes of varying length and sequence are studied in order to examine the effect of lengthening AT tracts on conversion of duplex to hairpins. The role of hairpin structure in dissociated strands is also examined and shown to be a necessary component of an effective switch. Insight into the conformation switch is obtained through binding studies of the different Zn(II) complexes to DNA oligonucleotides that contain unpaired thymines by using surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC).

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“…An alternative strategy that has been widely used for the recognition of bulges, abasic sites and mismatches is the use of coordination complexes. 6,[12][13][14][15] The metal ion centers in these complexes typically have a saturated coordination sphere and the complexes are kinetically inert towards ligand loss. [16][17][18][19] Aromatic heterocyclic ligands in these complexes facilitate interactions that involve stacking on nucleobases and shape recognition of the nucleic acid structure.…”

Section: Introductionmentioning

confidence: 99%

Bifunctional Zn(ii) complexes for recognition of non-canonical thymines in DNA bulges and G-quadruplexes

et al. 2015

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Six Zn(II) complexes of derivatives of 1,4,7,10-tetraazacyclododecane (cyclen) were studied for binding to DNA sequences containing non-canonical thymines, including a hairpin with a single thymine bulge (T-bulge) and a G-quadruplex (H-telo) containing thymine loops. The cyclen-based macrocycles contained pendents with either two fused rings to give planar groups including quinolinone (QMC), coumarin (MCC) and quinoline (CQC) derivatives or a non-planar dansyl group (DSC). Macrocyclic complexes with three fused rings including an anthraquinone pendent (ATQ) were also studied. All Zn(II) complexes were stable in solution at micromolar concentrations and neutral pH with the Zn(L)(OH2) species prevailing for L = QMC and CQC at pH 7.5 and 100 mM NaCl. Immobilized T-bulge or H-telo G-quadruplex was used to study binding of the complexes by surface plasmon resonance (SPR) for several of the complexes. For the most part, data matched well with that obtained by isothermal calorimetry (ITC) and, for fluorescent complexes, by fluorescence titrations. Data showed that Zn(II) complexes containing planar aromatic pendents with two fused rings bound to T-bulge more tightly than complexes with non-planar pendents such as DSC. The H-telo DNA exhibited multiple binding sites for all complexes containing aromatic pendents. The complexes with two fused rings bound with low micromolar dissociation constants and two binding sites whereas a complex with three fused rings (ATQ) bound to three sites. This study shows that different pendent groups on Zn(II) cyclen complexes impart selectivity for recognition of non-canonical DNA structures.

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Recognition of thymine in DNA bulges by a Zn(ii) macrocyclic complex

Cited by 18 publications

References 37 publications

Syntheses of polypyridyl metal complexes and studies of their interaction with quadruplex DNA

Syntheses of polypyridyl metal complexes and studies of their interaction with quadruplex DNA

Zn(II) complexes that trigger a DNA conformational switch

Bifunctional Zn(ii) complexes for recognition of non-canonical thymines in DNA bulges and G-quadruplexes

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