Selective Binding of Zn
            <sup>2+</sup>
            Complexes to Non‐Canonical Thymine or Uracil in DNA or RNA

Siters, Kevin E.; Sander, Stephanie A.; Morrow, Janet R.

doi:10.1002/9781118869994.ch03

Cited by 4 publications

(6 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…50,57 The combination of variable Zn 2+ coordination and variable aromatic pendents can be used to tune the selectivity of the complex toward different nucleic acid structures. 47 For example, our work has shown that Zn 2+ macrocyclic complexes with planar heteroatom-containing pendent groups bind strongly to thymine bulges, whereas Zn 2+ complexes with nonplanar pendents such as Zn(DSC) do not. 57 Zn(DSC) has been shown to bind to single-stranded oligonucleotides as well as duplexes containing abasic sites with an adjacent thymine.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Recognition of thymine nucleobases by Zn 2+ macrocyclic complexes has been studied extensively by the Kimura group, although predominantly in single-stranded DNA. Zn 2+ macrocyclic complexes interact with thymine- or uracil-containing nucleic acids through binding to the deprotonated N3 site of the pyrimidine ring (N3 – ). , In order for the Zn 2+ complex to bind in this manner, the thymine or uracil groups must be in a noncannonical context so that their Watson–Crick face is accessible and not involved in base pairing. Kimura and co-workers studied the binding of mononuclear and dinuclear Zn 2+ complexes to single-stranded nucleic acids .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Selective Binding of Zn²⁺ Complexes to Human Telomeric G-Quadruplex DNA

2014

Self Cite

View full text Add to dashboard Cite

The Zn(2+) complex of 5-(1,4,7,10-tetraazacyclododecan-1-ylsulfonyl)-N,N-dimethylnaphthalen-1-amine, Zn(DSC), binds selectively to the biologically relevant human telomeric (H-Telo) G-quadruplex. An increase in the Zn(DSC) dansyl group fluorescence with a simultaneous shift in emission is consistent with the complex binding to H-Telo. The H-Telo G-quadruplex has two binding sites for Zn(DSC) with binding constants in the low micromolar range (2.5 μM). Isothermal calorimetric titrations confirm low micromolar dissociation constants with a 2:1 stoichiometry. The interaction between H-Telo and Zn(DSC) is highly pH-dependent, consistent with binding to the unpaired thymines in the G-quadruplex loops. As a result, Zn(DSC) selectively binds to H-Telo over duplex DNA. In contrast to Zn(2+), Fe(2+) and Co(2+) do not complex to the DSC macrocycle appreciably under the conditions of the experiment. The Cu(2+) complex of DSC does not interact measurably with the H-Telo G-quadruplex. Interestingly, the H-Telo-Zn(DSC) adduct self-assembles from its individual components at physiological pH and 100 mM KCl. The self-assembly feature, which is specific for the Zn(2+) ion, suggests that this system may be viable as a Zn(2+) sensor. Pentanucleotides were studied in order to better describe the binding of Zn(DSC) to thymine sequences. NMR studies were consistent with the binding of Zn(DSC) to thymine-containing oligonucleotides including CCTCC, CTTCC, and CTCTC. Studies showed that the dansyl group of Zn(DSC) interacts with thymines in CTTCC. Fluorescence spectroscopy and ITC data indicate that Zn(DSC) forms 2:1 adducts with thymines that are spaced (CTCTC) but not tandem thymines (CTTCC). These data are consistent with one Zn(DSC) complex binding to two separate loops in the G-quadruplex. A second Zn(2+) complex containing an acridine pendent, Zn(ACR), binds tightly to pentanucleotides with both tandem and spaced thymines. Zn(ACR) indiscriminately binds to both H-Telo and duplex DNA.

show abstract

Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Selective Binding of Zn²⁺ Complexes to Human Telomeric G-Quadruplex DNA

2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…Uracil is well documented as a metal-binding pharmacophore [ 89 , 90 , 91 ] with particular emphasis on its Zn +2 -binding abilities [ 92 , 93 ]. In the present work, uracil has been established as a bioisostere of the zinc-binding moiety benzenesulfonamide in our synthesized carbonic anhydrase inhibitors 10a–l .…”

Section: Resultsmentioning

confidence: 99%

Uracil as a Zn-Binding Bioisostere of the Allergic Benzenesulfonamide in the Design of Quinoline–Uracil Hybrids as Anticancer Carbonic Anhydrase Inhibitors

et al. 2022

View full text Add to dashboard Cite

A series of quinoline–uracil hybrids (10a–l) has been rationalized and synthesized. The inhibitory activity against hCA isoforms I, II, IX, and XII was explored. Compounds 10a–l demonstrated powerful inhibitory activity against all tested hCA isoforms. Compound 10h displayed the best selectivity profile with good activity. Compound 10d displayed the best activity profile with minimal selectivity. Compound 10l emerged as the best congener considering both activity (IC50 = 140 and 190 nM for hCA IX and hCA XII, respectively) and selectivity (S.I. = 13.20 and 9.75 for II/IX, and II/XII, respectively). The most active hybrids were assayed for antiproliferative and pro-apoptotic activities against MCF-7 and A549. In silico studies, molecular docking, physicochemical parameters, and ADMET analysis were performed to explain the acquired CA inhibitory action of all hybrids. A study of the structure–activity relationship revealed that bulky substituents at uracil N-1 were unfavored for activity while substituted quinoline and thiouracil were effective for selectivity.

show abstract

“…[13][14][15][16][17][18] Many of these examples have been developed by Morrow and coworkers who have made significant discoveries in this arena (only a few select references of this extensive work are cited here). [19][20][21] The lanthanide(III) ion series possess very attractive properties for hydrolytic cleavage, especially when compared with the transition metals, notably the absence of accessible redox chemistry, strong Lewis acidity, high coordination numbers and charge density and fast ligand-exchange rates. 22 The latter is very favourable from a reactant binding and product release viewpoint.…”

Section: Introductionmentioning

confidence: 99%

Tri- and tetra-substituted cyclen based lanthanide(iii) ion complexes as ribonuclease mimics: a study into the effect of log K_a, hydration and hydrophobicity on phosphodiester hydrolysis of the RNA-model 2-hydroxypropyl-4-nitrophenyl phosphate (HPNP)

2015

View full text Add to dashboard Cite

A series of tetra-substituted 'pseudo' dipeptide ligands of cyclen (1,4,7,10,-tetraazacyclododecane) and a tri-substituted 3'-pyridine ligand of cyclen, and the corresponding lanthanide(III) complexes were synthesised and characterised as metallo-ribonuclease mimics. All complexes were shown to promote hydrolysis of the phosphodiester bond of 2-hydroxypropyl-4-nitrophenyl phosphate (HPNP, τ 1/2 = 5.87 × 10 3 h), a well known RNA mimic. The La(III) and Eu(III) tri-substituted 3'-pyridine lanthanide(III) complexes being the most efficient in promoting such hydrolysis at pH 7.4 and at 37°C; with τ 1/2 = 1.67 h for La(III) and 1.74 h for Eu(III). The series was developed to provide the opportunity to investigate the consequences of altering the lanthanide(III) ion, coordination ability and hydrophobicity of a metallo-cavity on the rate of hydrolysis using the model phosphodiester, HPNP, at 37°C. To further provide information on the role that the log K a of the metal bound water plays in phosphodiester hydrolysis the protonation constants and the metal ion stability constants of both a tri and tetra-substituted 3'pyridine complex were determined.Our results highlighted several key features for the design of lanthanide(III) ribonucelase mimics; the presence of two metal bound water molecules are vital for pH dependent rate constants for Eu(III) complexes, optimal pH activity approximating physiological pH (∼7.4) may be achieved if the log K a values for both MLOH and ML(OH) 2 species occur in this region, small changes to hydrophobicity within the metallo cavity influence the rate of hydrolysis greatly and an amide adjacent to the metal ion capable of forming hydrogen bonds with the substrate is required for achieving fast hydrolysis.

show abstract

Selective Binding of Zn ²⁺ Complexes to Non‐Canonical Thymine or Uracil in DNA or RNA

Cited by 4 publications

References 88 publications

Selective Binding of Zn²⁺ Complexes to Human Telomeric G-Quadruplex DNA

Selective Binding of Zn²⁺ Complexes to Human Telomeric G-Quadruplex DNA

Uracil as a Zn-Binding Bioisostere of the Allergic Benzenesulfonamide in the Design of Quinoline–Uracil Hybrids as Anticancer Carbonic Anhydrase Inhibitors

Tri- and tetra-substituted cyclen based lanthanide(iii) ion complexes as ribonuclease mimics: a study into the effect of log K_a, hydration and hydrophobicity on phosphodiester hydrolysis of the RNA-model 2-hydroxypropyl-4-nitrophenyl phosphate (HPNP)

Contact Info

Product

Resources

About

Selective Binding of Zn 2+ Complexes to Non‐Canonical Thymine or Uracil in DNA or RNA

Cited by 4 publications

References 88 publications

Selective Binding of Zn2+ Complexes to Human Telomeric G-Quadruplex DNA

Selective Binding of Zn2+ Complexes to Human Telomeric G-Quadruplex DNA

Uracil as a Zn-Binding Bioisostere of the Allergic Benzenesulfonamide in the Design of Quinoline–Uracil Hybrids as Anticancer Carbonic Anhydrase Inhibitors

Tri- and tetra-substituted cyclen based lanthanide(iii) ion complexes as ribonuclease mimics: a study into the effect of log Ka, hydration and hydrophobicity on phosphodiester hydrolysis of the RNA-model 2-hydroxypropyl-4-nitrophenyl phosphate (HPNP)

Contact Info

Product

Resources

About

Selective Binding of Zn ²⁺ Complexes to Non‐Canonical Thymine or Uracil in DNA or RNA

Selective Binding of Zn²⁺ Complexes to Human Telomeric G-Quadruplex DNA

Selective Binding of Zn²⁺ Complexes to Human Telomeric G-Quadruplex DNA

Tri- and tetra-substituted cyclen based lanthanide(iii) ion complexes as ribonuclease mimics: a study into the effect of log K_a, hydration and hydrophobicity on phosphodiester hydrolysis of the RNA-model 2-hydroxypropyl-4-nitrophenyl phosphate (HPNP)