Ammonium ion at low concentration stabilizes the G-quadruplex formation by telomeric sequence

Nagesh, Narayana; Chatterji, Dipankar

doi:10.1016/0165-022x(94)00057-k

Cited by 49 publications

(34 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nucleic acid quadruplexes based on the guanine quartet are stabilized not only by monovalent cations such as K + , Na + and

{NH}_{4}^{+}

(43), but also by certain divalent cations such as Pb 2+ (44), Sr 2+ (45,46) and Ba 2+ (43). With the purpose of exploring the effect of different metals on the unimolecular quadruplex conformations of the human telomere sequence, we determined CD spectra of HT2 in K + , Na + , Pb 2+ or Ba 2+ ions (Figure 4a).…”

Section: Resultsmentioning

confidence: 99%

Covalent ligation studies on the human telomere quadruplex

Shafer

2005

Nucleic Acids Research

View full text Add to dashboard Cite

Recent X-ray crystallographic studies on the human telomere sequence d[AGGG(TTAGGG)3] revealed a unimolecular, parallel quadruplex structure in the presence of potassium ions, while earlier NMR results in the presence of sodium ions indicated a unimolecular, antiparallel quadruplex. In an effort to identify and isolate the parallel form in solution, we have successfully ligated into circular products the single-stranded human telomere and several modified human telomere sequences in potassium-containing solutions. Using these sequences with one or two terminal phosphates, we have made chemically ligated products via creation of an additional loop. Circular products have been identified by polyacrylamide gel electrophoresis, enzymatic digestion with exonuclease VII and electrospray mass spectrometry in negative ion mode. Optimum pH for the ligation reaction of the human telomere sequence ranges from 4.5 to 6.0. Several buffers were also examined, with MES yielding the greatest ligation efficiency. Human telomere sequences with two phosphate groups, one each at the 3′ and 5′ ends, were more efficient at ligation, via pyrophosphate bond formation, than the corresponding sequences with only one phosphate group, at the 5′ end. Circular dichroism spectra showed that the ligation product was derived from an antiparallel, single-stranded guanine quadruplex rather than a parallel single-stranded guanine quadruplex structure.

show abstract

“…Nucleic acid quadruplexes based on the guanine quartet are stabilized not only by monovalent cations such as K + , Na + and

{NH}_{4}^{+}

Section: Resultsmentioning

confidence: 99%

Covalent ligation studies on the human telomere quadruplex

Shafer

2005

Nucleic Acids Research

View full text Add to dashboard Cite

show abstract

“…Nitrogen-containing ligands like TMPyP4, BRACO-19, Telomestatin etc., were found to be efficient in stabilizing quadruplex DNA and controlling tumor cell proliferation [23]–[27]. We have earlier reported the interaction and stabilization of quadruplex DNA by several nitrogen-containing ligands [28]–[31].…”

Section: Introductionmentioning

confidence: 99%

Phenyl 1,2,3-Triazole-Thymidine Ligands Stabilize G-Quadruplex DNA, Inhibit DNA Synthesis and Potentially Reduce Tumor Cell Proliferation over 3′-Azido Deoxythymidine

et al. 2013

Self Cite

View full text Add to dashboard Cite

Triazoles are known for their non-toxicity, higher stability and therapeutic activity. Few nucleoside (L1, L2 and L3) and non-nucleoside 1,2,3-triazoles (L4–L14) were synthesised using click chemistry and they were screened for tumor cell cytotoxicity and proliferation. Among these triazole ligands studied, nucleoside ligands exhibited higher potential than non-nucleoside ligands. The nucleoside triazole analogues, 3′-Phenyl-1,2,3- triazole-thymidine (L2) and 3′-4-Chlorophenyl-1,2,3-triazole-thymidine (L3), demonstrated higher cytotoxicity in tumor cells than in normal cells. The IC50 value for L3 was lowest (50 µM) among the ligands studied. L3 terminated cell cycle at S, G2/M phases and enhanced sub-G1 populations, manifesting induction of apoptosis in tumor cells. Confocal studies indicated that nucleoside triazole ligands (L2/L3) cause higher DNA fragmentation than other ligands. Preclinical experiments with tumor-induced mice showed greater reduction in tumor size with L3. In vitro DNA synthesis reaction with L3 exhibited higher DNA synthesis inhibition with quadruplex forming DNA (QF DNA) than non quadruplex forming DNA (NQF DNA). Tm of quadruplex DNA increased in the presence of L3, indicating its ability to enhance stability of quadruplex DNA at elevated temperature and the results indicate that it had higher affinity towards quadruplex DNA than the other forms of DNA (like dsDNA and ssDNA). From western blot experiment, it was noticed that telomerase expression levels in the tissues of tumor-induced mice were found to be reduced on L3 treatment. Microcalorimetry results emphasise that two nucleoside triazole ligands (L2/L3) interact with quadruplex DNA with significantly higher affinity (Kd≈10−7 M). Interestingly the addition of an electronegative moiety to the phenyl group of L2 enhanced its anti-proliferative activity. Though IC50 values are not significantly low with L3, the studies on series of synthetic 1,2,3-triazole ligands are useful for improving and building potential pro-apoptotic ligands.

show abstract

“…Upon the discovery that quadruplexes form in the presence of NH 4 + [34][35][36][37][38], a door was opened for quadruplex studies with mass spectrometry. Recently, ESI-MS studies have illustrated that stoichiometrics suggestive of Gquadruplexes have been sprayed from solution and persist in the solvent-free environment of the mass spectrometer [39][40][41][42][43][44][45].…”

Section: Scheme 1 (A) the Structure Of A G-quartet The Different Stmentioning

confidence: 99%

G-quadruplexes in telomeric repeats are conserved in a solvent-free environment

Baker

Bernstein

Gabelica

et al. 2006

International Journal of Mass Spectrometry

114

View full text Add to dashboard Cite

The structural properties of G-quadruplex forming sequences, such as the human telomeric repeat d(T 2 AG 3 ) n , are of great interest due to their role in cancer and cellular aging. To determine if G-quadruplexes are present in a sol vent-free environment, different lengths of the telomeric repeat d(T 2 AG 3 ) n (where n= 1, 2, 4 and 6) and dTG 4 T were investigated with mass spectrometry, ion mobility and molecular dynamics calculations. Nano-ESI-MS illustrated quadruplex stoichiometries compatible with G-quadruplex structures for each sequence, with dT 2 AG 3 and dTG 4 T forming 4-strand complexes with two and three NH 4 + adducts, d(T 2 AG 3 ) 2 a 2-strand complex, and d(T 2 AG 3 ) 4 and d(T 2 AG 3 ) 6 remaining single-stranded. Experimental cross sections were obtained for all species using ion mobility methods. In all cases, these could be quantitatively matched to model cross sections with specific strand orientations (parallel/antiparallel) and structures. For each species, the solvent-free structures agreed with the solution CD measurements, but the ion mobility/modeling procedure often gave much more detailed structural information.

show abstract

Ammonium ion at low concentration stabilizes the G-quadruplex formation by telomeric sequence

Cited by 49 publications

References 14 publications

Covalent ligation studies on the human telomere quadruplex

Covalent ligation studies on the human telomere quadruplex

Phenyl 1,2,3-Triazole-Thymidine Ligands Stabilize G-Quadruplex DNA, Inhibit DNA Synthesis and Potentially Reduce Tumor Cell Proliferation over 3′-Azido Deoxythymidine

G-quadruplexes in telomeric repeats are conserved in a solvent-free environment

Contact Info

Product

Resources

About