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Article ; Online: Enhancement of the thermal stability of G-quadruplex structures by urea.

Tariq, Nabeel / Xu, Christine / Wang, Jingtong / Kume, Takuma / Macgregor, Robert B

2023 Volume 299, Page(s) 107043

Abstract: ... In previous research, the solute has been shown to strongly destabilize folded G-quadruplex DNA structures ... This contribution demonstrates the stabilizing effect of urea on the G-quadruplex formed ... we investigated. The folded structure of G3T has three G-tetrads and three loops that consist of single thymine ...

Abstract	The solute urea has been used extensively as a denaturant in protein folding studies; double-stranded nucleic acid structures are also destabilized by urea, but comparatively less than proteins. In previous research, the solute has been shown to strongly destabilize folded G-quadruplex DNA structures. This contribution demonstrates the stabilizing effect of urea on the G-quadruplex formed by the oligodeoxyribonucleotide (ODN), G3T (d[5'-GGGTGGGTGGGTGGG-3']), and related sequences in the presence of sodium or potassium cations. Stabilization is observed up to 7 M urea, which was the highest concentration we investigated. The folded structure of G3T has three G-tetrads and three loops that consist of single thymine residues. ODNs related to G3T, in which the thymine residues in the loop are substituted by adenosine residues, also exhibit enhanced stability in the presence of molar concentrations of urea. The circular dichroism (CD) spectra of these ODNs in the presence of urea are consistent with that of a G-quadruplex. As the urea concentration increases, the spectral intensities of the peaks and troughs change, while their positions change very little. The heat-induced transition from the folded to unfolded state, T
MeSH term(s)	G-Quadruplexes ; Urea ; Thymine/chemistry ; Thermodynamics ; DNA/chemistry ; Circular Dichroism ; Nucleic Acid Conformation
Chemical Substances	Urea (8W8T17847W) ; Thymine (QR26YLT7LT) ; DNA (9007-49-2)
Language	English
Publishing date	2023-05-27
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	185052-0
ISSN	1873-4200 ; 0301-4622
ISSN (online)	1873-4200
ISSN	0301-4622
DOI	10.1016/j.bpc.2023.107043
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Article: The Pressure Dependence of the Stability of the G-quadruplex Formed by d(TGGGGT).

Tariq, Nabeel / Kume, Takuma / Feroze, Ujala N / Macgregor, Robert B

Life (Basel, Switzerland)

2022 Volume 12, Issue 5

Abstract: The G-quadruplex (GQ), a tetrahelix formed by guanine-rich nucleic acid sequences, is a potential ...

Abstract	The G-quadruplex (GQ), a tetrahelix formed by guanine-rich nucleic acid sequences, is a potential drug target for several diseases. Monomolecular GQs are stabilized by guanine tetrads and non-guanine regions that form loops. Hydrostatic pressure destabilizes the folded, monomolecular GQ structures. In this communication, we present data on the effect of pressure on the conformational stability of the tetramolecular GQ, d[5'-TGGGGT-3']
Language	English
Publishing date	2022-05-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life12050765
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Article ; Online: Dimethyl sulfoxide (DMSO) is a stabilizing co-solvent for G-quadruplex DNA.

Tariq, Nabeel / Kume, Takuma / Luo, Lingyan / Cai, Ziwei / Dong, Sihan / Macgregor, Robert B

Biophysical chemistry

2022 Volume 282, Page(s) 106741

Abstract: We report the effect of dimethyl sulfoxide (DMSO) on the stability of the four-stranded structures formed by the oligodeoxyribonucleotides d[5'-AGGG(TTAGGG) ...

Abstract	We report the effect of dimethyl sulfoxide (DMSO) on the stability of the four-stranded structures formed by the oligodeoxyribonucleotides d[5'-AGGG(TTAGGG)
MeSH term(s)	DNA/chemistry ; Dimethyl Sulfoxide ; G-Quadruplexes ; Nucleic Acid Conformation ; Solvents ; Urea/chemistry
Chemical Substances	Solvents ; Urea (8W8T17847W) ; DNA (9007-49-2) ; Dimethyl Sulfoxide (YOW8V9698H)
Language	English
Publishing date	2022-01-10
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	185052-0
ISSN	1873-4200 ; 0301-4622
ISSN (online)	1873-4200
ISSN	0301-4622
DOI	10.1016/j.bpc.2021.106741
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Article ; Online: Reducing daily salt intake in China by 1 g could prevent almost 9 million cardiovascular events by 2030: a modelling study.

Tan, Monique / He, Feng / Morris, Joan K / MacGregor, Graham

BMJ nutrition, prevention & health

2022 Volume 5, Issue 2, Page(s) 164–170

Abstract: Introduction: In China, salt intake is among the highest in the world (~11 g/day) and ... g/day could lower the risk for ischaemic heart disease by about 4% (95% uncertainty interval 1.8%-7 ... the Chinese government's target of ≤5 g/day by 2030, could prevent ~1.5 or 2 times more CVD events and deaths ...

Abstract	Introduction: In China, salt intake is among the highest in the world (~11 g/day) and cardiovascular disease (CVD) accounts for 40% of deaths. We estimated the potential impact of reducing salt intake on CVD events in China, via systolic blood pressure (SBP). Methods: To develop our model, we extracted the effect of salt reduction on SBP from a meta-regression of randomised trials and a population study, and that of SBP on CVD risk from pooled cohort studies. Results: Reducing population salt intake in China by 1 g/day could lower the risk for ischaemic heart disease by about 4% (95% uncertainty interval 1.8%-7.7%) and the risk for stroke by about 6% (2.4%-9.3%). Should this reduced salt level be sustained until 2030,~9 million (M) (7M-10.8M) CVD events could be prevented, of which ~4M (3.1M-4.9M) would have been fatal. Greater and gradual salt intake reductions, to achieve WHO's target of 30% reduction by 2025 or the Chinese government's target of ≤5 g/day by 2030, could prevent ~1.5 or 2 times more CVD events and deaths, respectively. Should the prolonged effect of salt reduction over several years be accounted for, all estimates of CVD events and deaths prevented would be 25% greater on average. Conclusion: Bringing down the high salt intake levels in China could result in large reductions in CVD. An easily achievable reduction of 1 g/day could prevent ~9M CVD events by 2030. Urgent action must be taken to reduce salt intake in China.
Language	English
Publishing date	2022-08-16
Publishing country	England
Document type	Journal Article
ISSN	2516-5542
ISSN (online)	2516-5542
DOI	10.1136/bmjnph-2021-000408
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Article ; Online: The Pressure Dependence of the Stability of the G-quadruplex Formed by d(TGGGGT)

Nabeel Tariq / Takuma Kume / Ujala N. Feroze / Robert B. Macgregor

Life, Vol 12, Iss 765, p

2022 Volume 765

Abstract: The G-quadruplex (GQ), a tetrahelix formed by guanine-rich nucleic acid sequences, is a potential ...

Abstract	The G-quadruplex (GQ), a tetrahelix formed by guanine-rich nucleic acid sequences, is a potential drug target for several diseases. Monomolecular GQs are stabilized by guanine tetrads and non-guanine regions that form loops. Hydrostatic pressure destabilizes the folded, monomolecular GQ structures. In this communication, we present data on the effect of pressure on the conformational stability of the tetramolecular GQ, d[5′-TGGGGT-3′] 4 . This molecule does not have loops linking the tetrads; thus, its physical properties presumably reflect those of the tetrads alone. Understanding the properties of the tetrads will aid in understanding the contribution of the other structural components to the stability of GQ DNA. By measuring UV light absorption, we have studied the effect of hydrostatic pressure on the thermal stability of the tetramolecular d[5′-TGGGGT-3′] 4 in the presence of sodium ions. Our data show that, unlike monomolecular GQ, the temperature at which d[5′-TGGGGT-3′] 4 dissociates to form the constituent monomers is nearly independent of pressure up to 200 MPa. This implies that there is no net molar volume difference (∆ V ) between the GQ and the unfolded random-coil states. This finding further suggests that the large negative ∆ V values for the unfolding of monomolecular GQ are due to the presence of the loop regions in those structures.
Keywords	G-quadruplex ; thermodynamics ; hydrostatic pressure ; volume ; CD spectroscopy ; Science ; Q
Subject code	660
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Measurement of the Q^{2} Dependence of the Deuteron Spin Structure Function g_{1} and its Moments at Low Q^{2} with CLAS.

Adhikari, K P / Deur, A / El Fassi, L / Kang, H / Kuhn, S E / Ripani, M / Slifer, K / Zheng, X / Adhikari, S / Akbar, Z / Amaryan, M J / Avakian, H / Ball, J / Balossino, I / Barion, L / Battaglieri, M / Bedlinskiy, I / Biselli, A S / Bosted, P /

Briscoe, W J / Brock, J / Bültmann, S / Burkert, V D / Thanh Cao, F / Carlin, C / Carman, D S / Celentano, A / Charles, G / Chen, J-P / Chetry, T / Choi, S / Ciullo, G / Clark, L / Cole, P L / Contalbrigo, M / Crede, V / D'Angelo, A / Dashyan, N / De Vita, R / De Sanctis, E / Defurne, M / Djalali, C / Dodge, G E / Drozdov, V / Dupre, R / Egiyan, H / El Alaoui, A / Elouadrhiri, L / Eugenio, P / Fedotov, G / Filippi, A / Ghandilyan, Y / Gilfoyle, G P / Golovatch, E / Gothe, R W / Griffioen, K A / Guidal, M / Guler, N / Guo, L / Hafidi, K / Hakobyan, H / Hanretty, C / Harrison, N / Hattawy, M / Heddle, D / Hicks, K / Holtrop, M / Hyde, C E / Ilieva, Y / Ireland, D G / Isupov, E L / Jenkins, D / Jo, H S / Johnston, S C / Joo, K / Joosten, S / Kabir, M L / Keith, C D / Keller, D / Khachatryan, G / Khachatryan, M / Khandaker, M / Kim, W / Klein, A / Klein, F J / Konczykowski, P / Kovacs, K / Kubarovsky, V / Lanza, L / Lenisa, P / Livingston, K / Long, E / MacGregor, I J D / Markov, N / Mayer, M / McKinnon, B / Meekins, D G / Meyer, C A / Mineeva, T / Mirazita, M / Mokeev, V / Movsisyan, A / Munoz Camacho, C / Nadel-Turonski, P / Niculescu, G / Niccolai, S / Osipenko, M / Ostrovidov, A I / Paolone, M / Pappalardo, L / Paremuzyan, R / Park, K / Pasyuk, E / Payette, D / Phelps, W / Phillips, S K / Pierce, J / Pogorelko, O / Poudel, J / Price, J W / Prok, Y / Protopopescu, D / Raue, B A / Rizzo, A / Rosner, G / Rossi, P / Sabatié, F / Salgado, C / Schumacher, R A / Sharabian, Y G / Shigeyuki, T / Simonyan, A / Skorodumina, Iu / Smith, G D / Sparveris, N / Sokhan, D / Stepanyan, S / Strakovsky, I I / Strauch, S / Sulkosky, V / Taiuti, M / Tan, J A / Ungaro, M / Voutier, E / Wei, X / Weinstein, L B / Zhang, J / Zhao, Z W

Physical review letters

2018 Volume 120, Issue 6, Page(s) 62501

Abstract: We measured the g_{1} spin structure function of the deuteron at low Q^{2}, where QCD can be ...

Abstract	We measured the g_{1} spin structure function of the deuteron at low Q^{2}, where QCD can be approximated with chiral perturbation theory (χPT). The data cover the resonance region, up to an invariant mass of W≈1.9 GeV. The generalized Gerasimov-Drell-Hearn sum, the moment Γ_{1}^{d} and the spin polarizability γ_{0}^{d} are precisely determined down to a minimum Q^{2} of 0.02 GeV^{2} for the first time, about 2.5 times lower than that of previous data. We compare them to several χPT calculations and models. These results are the first in a program of benchmark measurements of polarization observables in the χPT domain.
Language	English
Publishing date	2018-02-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	208853-8
ISSN	1079-7114 ; 0031-9007
ISSN (online)	1079-7114
ISSN	0031-9007
DOI	10.1103/PhysRevLett.120.062501
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Article ; Online: The role of loops and cation on the volume of unfolding of G-quadruplexes related to HTel.

Li, Yang Yun / Dubins, David N / Le, Dianna My Nhi Thi / Leung, Karen / Macgregor, Robert B

Biophysical chemistry

2017

Abstract: ... in guanine form four-stranded DNA structures called G-quadruplexes (G4s). These structures are destabilized ... are related to the G-rich ODN HTel (d[A(GGGTTA) ...

Abstract	In aqueous solutions containing sodium or potassium cations, oligodeoxyribonucleotides (ODNs) rich in guanine form four-stranded DNA structures called G-quadruplexes (G4s). These structures are destabilized by elevated hydrostatic pressure. Here, we use pressure to investigate the volumetric changes arising from the formation of G4 structures. G4s display a great deal of structural heterogeneity that depends on the stabilizing cation as well as the oligonucleotide sequence. Using UV thermal unfolding at different pressures, we have investigated the volume change of the helix-coil equilibrium of a series of ODNs whose sequences are related to the G-rich ODN HTel (d[A(GGGTTA)
Language	English
Publishing date	2017-01-06
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	185052-0
ISSN	1873-4200 ; 0301-4622
ISSN (online)	1873-4200
ISSN	0301-4622
DOI	10.1016/j.bpc.2016.12.003
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Book ; Online: Measurement of the omega -> pi^0 e^+e^- and eta -> e^+e^-g Dalitz decays with the A2 setup at MAMI

Adlarson, P. / Afzal, F. / Aguar-Bartolomé, P. / Ahmed, Z. / Annand, J. R. M. / Arends, H. J. / Bantawa, K. / Beck, R. / Berghäuser, H. / Biroth, M. / Borisov, N. S. / Braghieri, A. / Briscoe, W. J. / Cherepnya, S. / Cividini, F. / Collicott, C. / Costanza, S. / Danilkin, I. V. / Denig, A. /

Dieterle, M. / Downie, E. J. / Drexler, P. / Bondy, M. I. Ferretti / Fil'kov, L. V. / Gardner, S. / Garni, S. / Glazier, D. I. / Glowa, D. / Gradl, W. / Gurevich, G. M. / Hamilton, D. J. / Hornidge, D. / Huber, G. M. / Jude, T. C. / Käser, A. / Kashevarov, V. L. / Kay, S. / Keshelashvili, I. / Kondratiev, R. / Korolija, M. / Krusche, B. / Lazarev, A. / Linturi, J. / Lisin, V. / Livingston, K. / MacGregor, I. J. D. / Macrae, R. / Manley, D. M. / Martel, P. P. / McGeorge, J. C. / McNicoll, E. F. / Metag, V. / Middleton, D. G. / Miskimen, R. / Mornacchi, E. / Mullen, C. / Mushkarenkov, A. / Neganov, A. / Neiser, A. / Nikolaev, A. / Oberle, M. / Ostrick, M. / Ott, P. / Otte, P. B. / Paudyal, D. / Pedroni, P. / Polonski, A. / Prakhov, S. / Rajabi, A. / Robinson, J. / Ron, G. / Rosner, G. / Rostomyan, T. / Sfienti, C. / Sikora, M. H. / Sokhoyan, V. / Spieker, K. / Steffen, O. / Strakovsky, I. I. / Strandberg, B. / Strub, Th. / Supek, I. / Thiel, A. / Thiel, M. / Thomas, A. / Unverzagt, M. / Usov, Yu. A. / Wagner, S. / Walford, N. / Watts, D. P. / Werthmüller, D. / Wettig, J. / Witthauer, L. / Wolfes, M. / Zana, L. A.

2016

Abstract: The Dalitz decays eta -> e^+e^-g and omega -> pi^0 e^+e^- have been measured in the g p -> eta p ... and g p -> omega p reactions, respectively, with the A2 tagged-photon facility at the Mainz Microtron ... e^+e^-g and eta -> mu^+mu^-g decays. The uncertainty obtained in the value of Lambda^{-2}_eta is lower ...

Abstract	The Dalitz decays eta -> e^+e^-g and omega -> pi^0 e^+e^- have been measured in the g p -> eta p and g p -> omega p reactions, respectively, with the A2 tagged-photon facility at the Mainz Microtron, MAMI. The value obtained for the slope parameter of the electromagnetic transition form factor of eta, Lambda^{-2}_eta=(1.97+/-0.11_tot) GeV^{-2}, is in good agreement with previous measurements of the eta -> e^+e^-g and eta -> mu^+mu^-g decays. The uncertainty obtained in the value of Lambda^{-2}_eta is lower than in previous results based on the eta -> e^+e^-g decay. The value obtained for the omega slope parameter, Lambda^{-2}_omega_pi^0 = (1.99+/-0.21_tot) GeV^{-2}, is somewhat lower than previous measurements based on omega -> pi^0 mu^+mu^-, but the results for the omega transition form factor are in better agreement with theoretical calculations, compared to earlier experiments. Comment: 19 figures, 2 tables
Keywords	High Energy Physics - Experiment ; Nuclear Experiment
Subject code	551
Publishing date	2016-09-15
Publishing country	us
Document type	Book ; Online
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Article ; Online: Volumetric characterization of sodium-induced G-quadruplex formation.

Fan, Helen Y / Shek, Yuen Lai / Amiri, Amir / Dubins, David N / Heerklotz, Heiko / Macgregor, Robert B / Chalikian, Tigran V

Journal of the American Chemical Society

2011 Volume 133, Issue 12, Page(s) 4518–4526

Abstract: Oligodeoxyribonucleotides (ODN) with repeats of the human telomeric sequence can adopt different tetrahelical conformations that exhibit similar energetic parameters. We studied the volumetric properties of the folded and unfolded states of an ODN with ... ...

Abstract	Oligodeoxyribonucleotides (ODN) with repeats of the human telomeric sequence can adopt different tetrahelical conformations that exhibit similar energetic parameters. We studied the volumetric properties of the folded and unfolded states of an ODN with four repeats of the human telomeric sequence, d[A(GGGTTA)(3)GGG], by combining pressure-perturbation calorimetry (PPC), vibrating tube densimetry, ultrasonic velocimetry, and UV melting under high pressure. We carried out our volumetric measurements in aqueous buffers at pH 7 containing 20, 50, and 100 mM NaCl. All of the methods employed yielded volumetric parameters that were in excellent agreement. The molar volume changes, ΔV, of the conformational transition leading to formation of the folded state are large and positive. At 50 mM NaCl, the average transition volume, ΔV(tr), obtained from all the methods is 56.4 ± 3.5 cm(3) mol(-1) at the transition temperature of 47 °C, with ΔV(tr) decreasing with an increase in temperature. We carried out a molecular dynamics simulation of the change in the intrinsic geometric parameters of the ODN accompanying quadruplex formation. On the basis of the experimental and computational results, the folding transition of the ODN is accompanied by a release of 103 ± 44 water molecules from its hydration shell to the bulk. This number corresponds to ~18% of the net hydration of the coil conformation.
MeSH term(s)	Electrochemistry ; G-Quadruplexes ; Humans ; Models, Molecular ; Oligodeoxyribonucleotides/chemistry ; Sodium Chloride/chemistry
Chemical Substances	Oligodeoxyribonucleotides ; Sodium Chloride (451W47IQ8X)
Language	English
Publishing date	2011-03-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021/ja110495c
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Article ; Online: Quadruplex formation by both G-rich and C-rich DNA strands of the C9orf72 (GGGGCC)8•(GGCCCC)8 repeat: effect of CpG methylation.

Zamiri, Bita / Mirceta, Mila / Bomsztyk, Karol / Macgregor, Robert B / Pearson, Christopher E

Nucleic acids research

2015 Volume 43, Issue 20, Page(s) 10055–10064

Abstract: ... with unknown consequences. Typically, quadruplex structures form by G-rich but not complementary C-rich strands ... by G•C•G•C-tetrads and C•C•C•C-tetrads. Unlike G•G•G•G-tetrads, some G•C•G•C-tetrad conformations do ... hnRNPK, through band-shift analysis, bound C-rich but not G-rich strands, with a binding preference ...

Abstract	Unusual DNA/RNA structures of the C9orf72 repeat may participate in repeat expansions or pathogenesis of amyotrophic lateral sclerosis and frontotemporal dementia. Expanded repeats are CpG methylated with unknown consequences. Typically, quadruplex structures form by G-rich but not complementary C-rich strands. Using CD, UV and electrophoresis, we characterized the structures formed by (GGGGCC)8 and (GGCCCC)8 strands with and without 5-methylcytosine (5mCpG) or 5-hydroxymethylcytosine (5hmCpG) methylation. All strands formed heterogenous mixtures of structures, with features of quadruplexes (at pH 7.5, in K(+), Na(+) or Li(+)), but no feature typical of i-motifs. C-rich strands formed quadruplexes, likely stabilized by G•C•G•C-tetrads and C•C•C•C-tetrads. Unlike G•G•G•G-tetrads, some G•C•G•C-tetrad conformations do not require the N7-Guanine position, hence C9orf72 quadruplexes still formed when N7-deazaGuanine replace all Guanines. 5mCpG and 5hmCpG increased and decreased the thermal stability of these structures. hnRNPK, through band-shift analysis, bound C-rich but not G-rich strands, with a binding preference of unmethylated > 5hmCpG > 5mCpG, where methylated DNA-protein complexes were retained in the wells, distinct from unmethylated complexes. Our findings suggest that for C-rich sequences interspersed with G-residues, one must consider quadruplex formation and that methylation of quadruplexes may affect epigenetic processes.
MeSH term(s)	C9orf72 Protein ; CpG Islands ; Cytosine/chemistry ; DNA/chemistry ; DNA Methylation ; G-Quadruplexes ; Guanine/chemistry ; Heterogeneous-Nuclear Ribonucleoprotein K ; Humans ; Proteins/genetics ; Repetitive Sequences, Nucleic Acid ; Ribonucleoproteins/metabolism
Chemical Substances	C9orf72 Protein ; C9orf72 protein, human ; Heterogeneous-Nuclear Ribonucleoprotein K ; Proteins ; Ribonucleoproteins ; HNRNPK protein, human (146410-60-8) ; Guanine (5Z93L87A1R) ; Cytosine (8J337D1HZY) ; DNA (9007-49-2)
Language	English
Publishing date	2015-11-16
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkv1008
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