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GQW articles: June 2013 edition

201306GQW

Just a quick post with a list of 32 articles related to GQs published last June, roughly classified as follows:

  • (B). GQ-Biology: 6 articles
  • (C). GQ-Cations: 1 article
  • (M). GQ-Methods: 3 articles
  • (NT). GQ-Nano & Technology: 9 articles
  • (R). GQ-Recognition. 7 articles
  • (SD). GQ-Structure & Dynamics: 7 articles
  • (S). GQ-Supramolecular: 2 articles

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1. (B) Research shows four-stranded DNA in human cancer cells. Mayor S. Lancet Oncol. 2013 Mar; 14 (3): e91.  PMID: 23580959

2. (SD) A highly sensitive resonance Rayleigh scattering method to discriminate a parallel-stranded G-quadruplex from DNA with other topologies and structures. Shi Y, Luo HQ, Li NB. Chem Commun. 2013 Jun 4. [Epub] PMID: 23736799

3. (NT) A novel electrochemical aptasensor for thrombin detection based on the hybridization chain reaction with hemin/G-quadruplex DNAzyme-signal amplification. Zhang J, Chai Y, Yuan R, Yuan Y, Bai L, Xie S, Jiang L. Analyst. 2013 Jun 6. [Epub] PMID: 23741737

4. (B) Recognition of intermolecular G-quadruplexes by full length nucleophosmin. Effect of a leukaemia-associated mutation. Bañuelos S, Lectez B, Taneva SG, Ormaza G, Alonso-Mariño M, Calle X, Urbaneja MA. FEBS Lett. 2013 Jun 3. doi:pii: S0014-5793(13)00422-5. 10.1016/j.febslet.2013.05.055. [Epub] PMID: 23742937

5. (NT) Aptamer selection based on g4-forming promoter region. [OA] Yoshida W, Saito T, Yokoyama T, Ferri S, Ikebukuro K. PLoS One. 2013 Jun 4; 8 (6): e65497. doi: 10.1371/journal.pone.0065497. Print 2013. PMID: 23750264

6. (SD; M) Mechanical unfolding of long human telomeric RNA (TERRA). Garavís M, Bocanegra R, Herrero-Galán E, González C, Villasante A, Arias-Gonzalez JR. Chem Commun. 2013 Jun 10. [Epub] PMID: 23748212

7. (NT) A highly sensitive G-quadruplex-based luminescent switch-on probe for the detection of polymerase 3′-5′ proofreading activity. Surnameleung GH, Surnamehe GZ, Surnamezhong GJ, Surnamelu G, Surnamechan GS, Surnamema GL, Surnameleung GH. Methods. 2013 Jun 2. doi:pii: S1046-2023(13)00167-9. 10.1016/j.ymeth.2013.05.017. [Epub] PMID: 23748144

8. (B) Translational halt during elongation caused by G-quadruplex formed by mRNA. Endoh T, Kawasaki Y, Sugimoto N. Methods. 2013 Jun 6. doi:pii: S1046-2023(13)00192-8. 10.1016/j.ymeth.2013.05.026. [Epub] PMID: 23747335

9. (M) Clerocidin-mediated DNA footprinting discriminates among different G-quadruplex conformations and detects tetraplex folding in a duplex environment. Nadai M, Sattin G, Palù G, Palumbo M, Richter SN. Biochim Biophys Acta. 2013 Jun 6. doi:pii: S0304-4165(13)00243-2. 10.1016/j.bbagen.2013.05.039. [Epub] PMID: 23747297

10. (S) Quartet formation of a guanine derivative with an isopropyl group: crystal structures of “naked” G-quartets and thermodynamics of G-quartet formation. Inui Y, Shiro M, Fukuzumi S, Kojima T. Org Biomol Chem. 2013 Feb 7; 11 (5): 758-64. doi: 10.1039/c2ob26877a. Epub 2012 Dec 13. PMID: 23238354

11. (B) DNA2, a new player in telomere maintenance and tumor suppression. Chai W, Zheng L, Shen B. Cell Cycle. 2013 Jun 10; 12 (13). [Epub] PMID: 23759580

12. (NT; S) Guided assembly of tetramolecular G-quadruplexes. Yatsunyk LA, Pietrement O, Albrecht D, Tran PL, Renciuk D, Sugiyama H, Arbona JM, Aimé JP, Mergny JL. ACS Nano. 2013 Jun 13. [Epub] PMID: 23763613

13. (R) Pentose Phosphate Pathway Function Affects Tolerance to the G-Quadruplex Binder TMPyP4. [OA] Andrew EJ, Merchan S, Lawless C, Banks AP, Wilkinson DJ, Lydall D. PLoS One. 2013 Jun 12; 8 (6): e66242. doi: 10.1371/journal.pone.0066242. Print 2013. PMID: 23776642

14. (R) Spectroscopic and Biological Studies of Phenanthroline Compounds: Selective Recognition of Gene-Promoter G-Quadruplex DNAs Preferred over Duplex DNA. Wang L, Wei C. Chem Biodivers. 2013 Jun;10(6):1154-64. doi: 10.1002/cbdv.201200341. PMID: 23776031

15. (SD) Combination of i-Motif and G-Quadruplex Structures within the Same Strand: Formation and Application. Zhou J, Amrane S, Korkut DN, Bourdoncle A, He HZ, Ma DL, Mergny JL. Angew Chem Int Ed Engl. 2013 Jun 14. doi: 10.1002/anie.201301278. [Epub] PMID: 23775868

16. (SD) Folding thermodynamics of the hybrid-1 type intramolecular human telomeric G-quadruplex. Shek YL, Noudeh GD, Nazari M, Heerklotz H, Abu-Ghazalah RM, Dubins DN, Chalikian TV. Biopolymers. 2013 Jun 18. doi: 10.1002/bip.22317. [Epub] PMID: 23775839

17. (B) Mechanistic Studies for the Role of Cellular Nucleic-acid-binding Protein (CNBP) in Regulation of c-myc Transcription. Chen S, Su L, Qiu J, Xiao N, Lin J, Tan JH, Ou TM, Gu LQ, Huang ZS, Li D. Biochim Biophys Acta. 2013 Jun 14. doi:pii: S0304-4165(13)00267-5. 10.1016/j.bbagen.2013.06.007. [Epub] PMID: 23774591

18. (SD) Distance-dependent duplex DNA destabilization proximal to G-quadruplex/i-motif sequences. [OA] König SL, Huppert JL, Sigel RK, Evans AC. Nucleic Acids Res. 2013 Jun 14. [Epub] PMID: 23771141

19. (NT) A dual-functional electrochemical biosensor for the detection of prostate specific antigen and telomerase activity. Liu J, Lu CY, Zhou H, Xu JJ, Wang ZH, Chen HY. Chem Commun. 2013 Jun 14. [Epub] PMID: 23770709

20. (NT) A simple, fast and highly sensitive assay for the detection of telomerase activity. Quach QH, Jung J, Kim H, Chung BH. Chem Commun. 2013 Jun 14. [Epub]  PMID: 23770610

21. (NT) A label-free DNA hairpin biosensor for colorimetric detection of target with suitable functional DNA partners. Nie J, Zhang DW, Tie C, Zhou YL, Zhang XX. Biosens Bioelectron. 2013 May 25;49C:236-242. doi: 10.1016/j.bios.2013.05.020. [Epub]  PMID: 23770395

22. (R) The influence of positional isomerism on G-quadruplex binding and anti-proliferative activity of tetra-substituted naphthalene diimide compounds. Mpima S, Ohnmacht SA, Barletta M, Husby J, Pett LC, Gunaratnam M, Hilton ST, Neidle S. Bioorg Med Chem. 2013 May 25. doi:pii: S0968-0896(13)00463-X. 10.1016/j.bmc.2013.05.027. [Epub] PMID: 23769166

23. (SD) Excimer Formation by Stacking G-Quadruplex Blocks. Dao NT, Haselsberger R, Michel-Beyerle ME, Phan AT. ChemPhysChem. 2013 Jun 18. doi: 10.1002/cphc.201300481. [Epub] PMID: 23780713

24. (M) A novel microfluidic mixer based on dual-hydrodynamic focusing for interrogating the kinetics of DNA-protein interaction. Li Y, Xu F, Liu C, Xu Y, Feng X, Liu BF. Analyst. 2013 Jun 20. [Epub] PMID: 23785706

25. (B) G-Quadruplex DNA as a Molecular Target for Induced Synthetic Lethality in Cancer Cells. McLuckie KI, Di Antonio M, Zecchini H, Xian J, Caldas C, Krippendorff BF, Tannahill D, Lowe C, Balasubramanian S. J Am Chem Soc. 2013 Jun 19. [Epub] PMID: 23782415

26. (R) Macrocyclic biphenyl tetraoxazoles: Synthesis, evaluation as G-quadruplex stabilizers and cytotoxic activity. Blankson GA, Pilch DS, Liu AA, Liu LF, Rice JE, Lavoie EJ. Bioorg Med Chem. 2013 May 30. doi:pii: S0968-0896(13)00482-3. 10.1016/j.bmc.2013.05.033. [Epub] PMID: 23787291

27. (R) On the interaction between [Ru(NH3)6]3+ and the G-quadruplex forming thrombin binding aptamer sequence. De Rache A, Doneux T, Kejnovská I, Buess-Herman C. J Inorg Biochem. 2013 May 30;126C:84-90. doi: 10.1016/j.jinorgbio.2013.05.014. [Epub] PMID: 23787142

28. (R) V-Shaped Dinuclear Pt(II) Complexes: Selective Interaction with Human Telomeric G-quadruplex and Significant Inhibition towards Telomerase. [OA] Xu CX, Zheng YX, Zheng XH, Hu Q, Zhao Y, Ji LN, Mao ZW. Sci Rep. 2013 Jun 24;3:2060. doi: 10.1038/srep02060. PMID: 23792883

29. (NT; C) A “turn-on” fluorescent sensor for detection of Pb2+ based on graphene oxide and G-quadruplex DNA. Li X, Wang G, Ding X, Chen Y, Gou Y, Lu Y. Phys Chem Chem Phys. 2013 Jun 25. [Epub] PMID: 23799396

30. (SD) Polyethylene glycol binding alters human telomere G-quadruplex structure by conformational selection. [OA] Buscaglia R, Miller MC, Dean WL, Gray RD, Lane AN, Trent JO, Chaires JB. Nucleic Acids Res. 2013 Jun 26. [Epub] PMID: 23804761

31. (NT) Stable label-free fluorescent sensing of biothiols based on ThT direct inducing conformation-specific G-quadruplex. Tong LL, Li L, Chen Z, Wang Q, Tang B. Biosens Bioelectron. 2013 Jun 10; 49C: 420-425. doi: 10.1016/j.bios.2013.05.051. [Epub] PMID: 23807235

32. (R) Asymmetric distyrylpyridinium dyes as red-emitting fluorescent probes for quadruplex DNA. Xie X, Choi B, Largy E, Guillot R, Granzhan A, Teulade-Fichou MP. Chemistry. 2013 Jan 21; 19 (4): 1214-26. doi: 10.1002/chem.201203710. Epub 2013 Jan 4. PMID: 23292703

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Key:

  • (B). GQ-Biology: Studies aimed at the discovery of GQs in living organisms and the elucidation of their role in biological processes. (putative quadruplex sequences in genomes; proteins that recognize GQs; in vitro and in vivo studies of GQs).
  • (C). GQ-Cations: Studies aimed at elucidating the role of cations in the structure and/or dynamics of GQs.
  • (M). GQ-Methods: Application and development of methods and techniques to study GQs.
  • (NT). GQ-Nano & Technology: The design and development of GQ-based nanostructures. The use of GQs as components in devices (e.g., sensors, aptamers).
  • (R). GQ-Recognition.Discovery and development of (mostly) small molecule ligands that recognize GQs (synthesis; design; pharmacology; medicinal chemistry).
  • (SD). GQ-Structure & Dynamics: Studies aimed at elucidating structure and/or dynamics GQ. This includes experimental techniques such as X-Ray crystallography, NMR, and other spectroscopic methods as well as theoretical approaches such as MD-simulations.
  • (S). GQ-Supramolecular: Studies related to the design and applications of GQs in supramolecular chemistry. Of particular interest are studies on the use of independent guanosine subunits to guide the self-assembly of complex structures.
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GQW articles: March 2012 edition


From this post onwards, I intend to classify the monthly references by subtopics. Having the references curated this way makes the initial process a little more time consuming, but, I’m hoping it will pay out in the end by providing a quick reference source in the future.

The initial subtopics, with a basic description and some keywords/tags, are:

  • GQ-Biology. Studies aimed at the discovery of GQs in living organisms and the elucidation of their role in biological processes. (putative quadruplex sequences in genomes; proteins that recognize GQs; in vitro and in vivo studies of GQs)
  • GQ-Cations. Studies aimed at elucidating the role of cations in GQ structure and/or dynamics.
  • GQ-Methods. Application and development of methods and techniques to study GQs.
  • GQ-Nano & Technology. The design and development of GQ-based nanostructures. The use of GQs as components in devices (e.g., sensors; molecular machinery).
  • GQ-Recognition. Discovery and development of (mostly) small molecule ligands that recognize GQs (synthesis; design; pharmacology; medicinal chemistry).
  • GQ-Structure & Dynamics. Studies aimed at elucidating the detailed structure and/or dynamics of GQs. This includes experimental techniques such as X-Ray crystallography, NMR, and other spectroscopic methods as well as theoretical approaches such as MD-simulations.
  • GQ-Supramolecular. Studies related to the design and applications of GQs in supramolecular chemistry. Of particular interest are studies on the use of independent guanosine subunits to guide the self-assembly of complex structures. (assemblies; molecular devices)

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• GQ-Biology. Studies aimed at the discovery of GQs in living organisms and the elucidation of their role in biological processes. (putative quadruplex sequences in genomes; proteins that recognize GQs; in vitro and in vivo studies of GQs) [13 articles]


  1. The DEAH-box helicase RHAU is an essential gene and critical for mouse hematopoiesis. Lai JC, Ponti S, Pan D, Kohler H, Skoda RC, Matthias P, Nagamine Y. Blood. 2012 Mar 15. [Epub before print] PMID: 22422825
  2. The RNA helicase RHAU (DHX36) unwinds a G4-quadruplex in human telomerase RNA and promotes the formation of the P1 helix template boundary. [OA] E. P. Booy, M. Meier, N. Okun, S. K. Novakowski, S. Xiong, J. Stetefeld, & S. A. McKenna. Nucleic Acids Res. published 11 January 2012, 10.1093/nar/gkr1306
  3. Cell Cycle Regulation of G-Quadruplex DNA Structures at Telomeres. Juranek SA, Paeschke K. Curr Pharm Des.2012 Feb 27. [Epub before print] PMID: 22376109
  4. New insights into replication origin characteristics in metazoans. Cayrou C, Coulombe P, Puy A, Rialle S, Kaplan N, Segal E, Méchali M. Cell Cycle. 2012 Feb 15;11(4):658-67. PMID: 22373526
  5. The formation and stabilization of a novel G-quadruplex in the 5′-flanking region of the relaxin gene [OA] Lin S, Gu H, Xu M, Cui X, Zhang Y, Gao W, Yuan G. PLoS One. 2012;7(2):e31201. Epub 2012 Feb 21. PMID: 22363579
  6. Saccharomyces cerevisiae Mph1 helicase on junction-containing DNA structures [OA] Young-Hoon Kang, Palinda Ruvan Munashingha, Chul-Hwan Lee, Tuan Anh Nguyen, & Yeon-Soo Seo. Nucleic Acids Res. 2012; 40: 2089-2106.
  7. Nonspaced inverted DNA repeats are preferential targets for homology-directed gene repair in mammalian cells. [OA] Maarten Holkers, Antoine A. F. de Vries, and Manuel A. F. V. Gonçalves. Nucleic Acids Res. 2012; 40:1984-1999.
  8. Yin Yang 1 contains G-quadruplex structures in its promoter and 5′-UTR and its expression is modulated by G4 resolvase 1. [OA] Weiwei Huang, Philip J. Smaldino, Qiang Zhang, Lance D. Miller, Paul Cao, Kristin Stadelman, Meimei Wan, Banabihari Giri, Ming Lei, Yoshikuni Nagamine, James P. Vaughn, Steven A. Akman, & Guangchao Sui. Nucleic Acids Res. 2012; 40:1033-1049.
  9. Overcoming natural replication barriers: differential helicase requirements [OA] Ranjith P. Anand, Kartik A. Shah, Hengyao Niu, Patrick Sung, Sergei M. Mirkin, & Catherine H. Freudenreich. Nucleic Acids Res. 2012; 40:1091-1105.
  10. Quadruplex-single nucleotide polymorphisms (Quad-SNP) influence gene expression difference among individuals. [OA] Aradhita Baral, Pankaj Kumar, Rashi Halder, Prithvi Mani, Vinod Kumar Yadav, Ankita Singh, Swapan K. Das, & Shantanu Chowdhury. Nucleic Acids Res. published 11 January 2012, [Epub before print]
  11. Bisquinolinium compounds induce quadruplex-specific transcriptome changes in HeLa S3 cell lines. R Halder, JF Riou, MP Teulade-Fichou, T Frickey, & JS Hartig. BMC Res Notes. 2012; 5: 138.
  12. A telomerase-associated RecQ protein-like helicase resolves telomeric G-quadruplex structures during replication. J Postberg, M Tsytlonok, D Sparvoli, D Rhodes, & HJ Lipps. Gene. 2012. [Epub before print]
  13. DNA replication through hard-to-replicate sites, including both highly transcribed RNA Pol II and Pol III genes, requires the S. pombe Pfh1 helicase. N Sabouri, KR McDonald, CJ Webb, IM Cristea, & VA Zakian. Genes Dev. 2012; 26: 581.
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• GQ-Cations. Studies aimed at elucidating the role of cations in the structure and/or dynamics of GQs. [1 article]

  1. Kinetics and mechanism of G-quadruplex formation and conformational switch in a G-quadruplex of PS2.M induced by Pb2+ . Wei Liu, Hong Zhu, Bin Zheng, Sheng Cheng, Yan Fu, Wei Li, Tai-Chu Lau, and Haojun Liang. Nucleic Acids Res. published 12 January 2012, 10.1093/nar/gkr1310
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• GQ-Methods. Application and development of methods and techniques to study GQs. [11 articles]

  1. Determination of DNA structural detail using radioprobing. Girard PM, Laughton C, Nikjoo H. Int J Radiat Biol. 2012 Jan;88(1-2):123-128. Epub 2011 Sep 21. PMID: 21823822
  2. Tandem mass spectrometry of platinated quadruplex DNA. Stucki SR, Nyakas A, Schürch S. J Mass Spectrom. 2011 Dec;46 (12):1288-1297. doi: 10.1002/jms.2019. PMID: 22223421
  3. Selective isolation of G-quadruplexes by affinity chromatography. Chang T, Liu X, Cheng X, Qi C, Mei H, Shangguan D. J Chromatogr A. 2012 Feb 16. [Epub before print] PMID: 22398385
  4. Reporter assays for studying quadruplex nucleic acids. Halder K, Benzler M, Hartig JS. Methods. 2012 Feb 23. [Epub ahead of print] PMID: 22388183
  5. G-quadruplex structure and stability illuminated by 2-aminopurine phasor plots [OA] Robert Buscaglia, David M. Jameson, & Jonathan B. Chaires. Nucleic Acids Res. published 12 January 2012, 10.1093/nar/gkr1286
  6. Sensitive and label-free biosensing of RNA with predicted secondary structures by a triplex affinity capture method. Laura G. Carrascosa, S. Gómez-Montes, A. Aviñó, A. Nadal, M. Pla, R. Eritja, & L. M. Lechuga. Nucleic Acids Res. published 12 January 2012, 10.1093/nar/gkr1304
  7. A streptavidin paramagnetic-particle based competition assay for the evaluation of the optical selectivity of quadruplex nucleic acid fluorescent probes. E Largy, F Hamon, & MP Teulade-Fichou. Methods. 2012. [Epub before print]
  8. Methods of studying telomere damage induced by quadruplex-ligand complexes. Rizzo A, Salvati E, Biroccio A. Methods. 2012 Mar 4. [Epub before print] PMID: 22410593
  9. Fluorescence properties of 8-(2-pyridyl)guanine “2PyG” as compared to 2-aminopurine in DNA. Dumas A, Luedtke NW. Chembiochem. 2011 Sep 5;12(13):2044-51. doi: 10.1002/cbic.201100214. Epub 2011 Jul 22. PMID: 21786378
  10. Circular dichroism and guanine quadruplexes. M Vorlickova, I Kejnovska, J Sagi, D Renciuk, K Bednarova, J Motlova, & J Kypr. Methods. 2012. [Epub before print]
  11. Combination of chromatographic and chemometric methods to study the interactions between DNA strands. S Ruiz-Castelar, A Checa, R Gargallo, & J Jaumot. Anal Chim Acta. 2012; 722: 34. PMID: 22444532
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• GQ-Nano & Technology.  The design and development of GQ-based nanostructures. The use of GQs as components in devices (e.g., sensors, aptamers). [17 articles]

  1. Hemin/G-quadruplex simultaneously acts as NADH oxidase and HRP-mimicking DNAzyme for simple, sensitive pseudobienzyme electrochemical detection of thrombin. Yuan Y, Yuan R, Chai Y, Zhuo Y, Ye X, Gan X, Bai L. Chem Commun. 2012 Mar 30. [Epub before print] PMID: 22466956
  2. DNAzyme-based turn-on chemiluminescence assays in homogenous media. Zhou M, Liu Y, Tu Y, Tao G, Yan. J. Biosens Bioelectron. 2012 Mar 17. [Epub before print] PMID: 22465444
  3. Label-free Fluorescent Detection of Ions, Proteins and Small Molecules Using Structure-Switching Aptamers, SYBR Gold and Exonuclease Ⅰ. Zheng D, Zou R, Lou X. Anal Chem. 2012 Mar 16. [Epub before print]  PMID: 22424113
  4. The insertion of two 8-methyl-2′-deoxyguanosine residues in tetramolecular quadruplex structures: trying to orientate the strands. [OA] Virgilio A, Esposito V, Citarella G, Pepe A, Mayol L, Galeone A. Nucleic Acids Res. 2012 Jan; 40 (1):461-75. Epub 2011 Sep 9. PMID: 21908403
  5. Elongated Thrombin Binding Aptamer: A G-Quadruplex Cation-Sensitive Conformational Switch. De Rache A, Kejnovská I, Vorlíčková M, Buess-Herman C. Chemistry. 2012 Feb 23. doi: 10.1002/chem.201103381. [Epub ahead of print] PMID: 22362492
  6. Amplified Surface Plasmon Resonance and Electrochemical Detection of Pb2+ Ions Using the Pb2+-Dependent DNAzyme and Hemin/G-Quadruplex as a Label. Pelossof G, Tel-Vered R, Willner I. Anal Chem. 2012 Mar 15. [Epub ahead of print] PMID: 22424055
  7. A G-quadruplex based label-free fluorescent biosensor for lead ion. Guo L, Nie D, Qiu C, Zheng Q, Wu H, Ye P, Hao Y, Fu F, Chen G. Biosens Bioelectron. 2012 Feb 24. [Epub before print] PMID: 22417873
  8. G-Quadruplex as Signal Transducer for Biorecognition Events. Lv L, Guo Z, Wang J, Wang E. Curr Pharm Des. 2012 Feb 27. [Epub ahead of print] PMID: 22380517
  9. G-Quadruplex Based Probes for Visual Detection and Sensing. Neo JL, Kamaladasan K, Uttamchandani M. Curr Pharm Des. 2012 Feb 27. [Epub before print] PMID: 22380516
  10. G-quadruplex DNA Aptamers and their Ligands: Structure, Function and Application. Tucker WO, Shum KT, Tanner JA. Curr Pharm Des. 2012 Feb 27. [Epub before print] PMID: 22376117
  11. A label-free, G-quadruplex DNAzyme-based fluorescent probe for signal-amplified DNA detection and turn-on assay of endonuclease. Zhou Z, Du Y, Zhang L, Dong S. Biosens Bioelectron. 2012 Jan 28. [Epub ahead of print] PMID: 22366377
  12. A label-free fluorescence DNA probe based on ligation reaction with quadruplex formation for highly sensitive and selective detection of nicotinamide adenine dinucleotide. J Zhao, L Zhang, J Jiang, G Shen, and R Yu. Chem Commun. 2012.
  13. Label-free Fluorescent Detection of Ions, Proteins and Small Molecules Using Structure-Switching Aptamers, SYBR Gold and Exonuclease. D Zheng, R Zou, and X Lou. Anal Chem. 2012. [Epub before print]
  14. G-Quadruplex as Signal Transducer for Biorecognition Events. L Lv, Z Guo, J Wang, and E Wang. Curr Pharm Des. 2012. [Epub before print]
  15. G-quadruplex DNA Aptamers and their Ligands: Structure, Function and Application. WO Tucker, KT Shum, and JA Tanner. Curr Pharm Des. 2012. [Epub before print]
  16. A novel biosensing strategy for screening G-quadruplex ligands based on graphene oxide sheets. H Wang, T Chen, S Wu, X Chu, and R Yu. Biosens Bioelectron. 2012. [Epub before print]
  17. Single strand DNA catenane synthesis using the formation of G-quadruplex structure. Sannohe Y, Sugiyama H. Bioorg Med Chem. 2012 Feb 1. [Epub before print] PMID: 22364954
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• GQ-Recognition. Discovery and development of (mostly) small molecule ligands that recognize GQs (ynthesis; design; pharmacology; medicinal chemistry). [29 articles]


  1. Dimeric 1,3-Phenylene-bis(piperazinyl benzimidazole)s: Synthesis and Structure-Activity Investigations on their Binding with Human Telomeric G-Quadruplex DNA and Telomerase Inhibition Properties. Jain AK, Paul A, Maji B, Muniyappa K, Bhattacharya S. J Med Chem. 2012 Mar 27. [Epub ahead of print]PMID: 22452380
  2. Molecular basis of structure-activity relationships between salphen metal complexes and human telomeric DNA quadruplexes. Campbell NH, Karim NH, Parkinson GN, Gunaratnam M, Petrucci V, Todd AK, Vilar R, Neidle S. J Med Chem. 2012 Jan 12; 55 (1):209-222. Epub 2011 Dec 13. PMID: 22112241
  3. Structural polymorphism of human telomere G-quadruplex induced by a pyridyl carboxamide molecule. Xu L, Xu Z, Shang Y, Feng S, Zhou X. Bioorg Med Chem Lett. 2012 Feb 28. [Epub ahead of print] PMID: 22440628
  4. A Caged Ligand for a Telomeric G-Quadruplex. Nakamura T, Iida K, Tera M, Shin-Ya K, Seimiya H, Nagasawa K. Chembiochem. 2012 Mar 21. doi: 10.1002/cbic.201200013. [Epub ahead of print] PMID: 22438312
  5. Structure, function and targeting of human telomere RNA. Xu Y, Komiyama M. Methods. 2012 Mar 8. [Epub ahead of print] PMID: 22425636
  6. G-quadruplexes: targets and tools in anticancer drug design. Düchler M. J Drug Target. 2012 Mar 19. [Epub ahead of print] PMID: 22424091
  7. Identification of novel telomeric G-quadruplex-targeting chemical scaffolds through screening of three NCI libraries. Rahman KM, Tizkova K, Reszka AP, Neidle S, Thurston DE. Bioorg Med Chem Lett. 2012 Feb 16. [Epub ahead of print] PMID: 22421021
  8. Bisquinolinium compounds induce quadruplex-specific transcriptome changes in HeLa S3 cell lines. Halder R, Riou JF, Teulade-Fichou MP, Frickey T, Hartig JS. BMC Res Notes. 2012 Mar 13;5(1):138. [Epub ahead of print] PMID: 22414013
  9. Spectroscopic probing of recognition of the G-quadruplex in c-kit promoter by small-molecule natural products. Cui X, Lin S, Yuan G. Int J Biol Macromol. 2012 Mar 3. [Epub ahead of print] PMID: 22405847
  10. In silico screening of quadruplex-binding ligands. Ma DL, Ma VP, Chan DS, Leung KH, Zhong HJ, Leung CH. Methods. 2012 Feb 26. [Epub ahead of print] PMID: 22391485
  11. Heterocyclic Dications as a New Class of Telomeric G-Quadruplex Targeting Agents.  Nanjunda R, Musetti C, Kumar A, Ismail MA, Farahat AA, Wang S, Sissi C, Palumbo M, Boykin DW, Wilson WD. Curr Pharm Des. 2012 Feb 27. [Epub ahead of print] PMID: 22380518
  12. Synthesis of Small Molecules Targeting Multiple DNA Structures using Click Chemistry. Howell LA, Bowater RA, O’Connell MA, Reszka AP, Neidle S, Searcey M. ChemMedChem. 2012 Feb 29. doi: 10.1002/cmdc.201200060. [Epub ahead of print] PMID: 22378532
  13. Human Telomere RNA: A Potential Target for Ligand Recognition. Xu Y. Curr Pharm Des. 2012 Feb 27. [Epub ahead of print] PMID: 22376119
  14. Screening of a Chemical Library by HT-G4-FID for Discovery of Selective G-quadruplex Binders. Largy E, Saettel N, Hamon F, Dubruille S, Teulade-Fichou MP. Curr Pharm Des. 2012 Feb 27. [Epub ahead of print] PMID: 22376118
  15. Searching Drug-like Anti-cancer Compound(s) Based on G-Quadruplex Ligands. Li Q, Xiang JF, Zhang H, Tang YL. Curr Pharm Des. 2012 Feb 27. [Epub ahead of print] PMID: 22376116
  16. The Polymorfisms of DNA G-Quadruplex investigated by Docking Experiments with Telomestatin Enantiomers. Alcaro S, Costa G, Distinto S, Moraca F, Ortuso F, Parrotta L, Artese A. Curr Pharm Des. 2012 Feb 27. [Epub ahead of print] PMID: 22376115
  17. G-Quadruplex Binding Ligands: from Naturally Occurring to Rationally Designed Molecules. Le TV, Han S, Chae J, Park HJ. Curr Pharm Des. 2012 Feb 27. [Epub ahead of print] PMID: 22376113
  18. Targeting DNA G-Quadruplex Structures with Peptide Nucleic Acids. Panyutin IG, Onyshchenko MI, Englund EA, Appella DH, Neumann RD. Curr Pharm Des. 2012 Feb 27. [Epub ahead of print] PMID: 22376112
  19. Luminescent G-quadruplex Probes. Ma DL, Chan DS, Yang H, He HZ, Leung CH. Curr Pharm Des. 2012 Feb 27. [Epub ahead of print] PMID: 22376110
  20. Experimental Methods for Studying the Interactions between G-Quadruplex Structures and Ligands Jaumot J, Gargallo R. Curr Pharm Des. 2012 Feb 27. [Epub ahead of print] PMID: 22376108
  21. Structure Conversion and Structure Separation of G-Quadruplexes Investigated by Carbazole Derivatives. Chang TC, Chu JF, Tsai YL, Wang ZF. Curr Pharm Des. 2012 Feb 27. [Epub ahead of print] PMID: 22376106
  22. Recent Developments in the Chemistry and Biology of G-Quadruplexes with Reference to the DNA Groove Binders. Jain AK, Bhattacharya S. Curr Pharm Des. 2012 Feb 27. [Epub ahead of print] PMID: 22376105
  23. State-of-the-Art Methodologies for the Discovery and Characterization of DNA G-Quadruplex Binder. Pagano B, Cosconati S, Gabelica V, Petraccone L, De Tito S, Marinelli L, La Pietra V, di Leva FS, Lauri I, Trotta R, Novellino E, Giancola C, Randazzo A. Curr Pharm Des. 2012 Feb 27. [Epub ahead of print] PMID: 22376104
  24. Stabilization of G-Quadruplex DNA, Inhibition of Telomerase Activity and Live Cell Imaging Studies of Chiral Ruthenium(II) Complexes. Sun D, Liu Y, Liu D, Zhang R, Yang X, Liu J. Chemistry. 2012 Feb 24. doi: 10.1002/chem.201103156. [Epub ahead of print] PMID: 22367788
  25. Hybrid ligand-alkylating agents targeting telomeric G-quadruplex structures. Doria F, Nadai M, Folini M, Di Antonio M, Germani L, Percivalle C, Sissi C, Zaffaroni N, Alcaro S, Artese A, Richter SN, Freccero M. Org Biomol Chem. 2012 Feb 27. [Epub ahead of print] PMID: 22367401
  26. Interaction of human telomeric DNA with N-methyl mesoporphyrin IX. [OA] Nicoludis JM, Barrett SP, Mergny JL, Yatsunyk LA. Nucleic Acids Res. 2012 Feb 23. [Epub ahead of print] PMID: 22362740
  27. Luminescent detection of DNA-binding proteins [OA] Chung-Hang Leung, Daniel Shiu-Hin Chan, Hong-Zhang He, Zhen Cheng, Hui Yang, and Dik-Lung Ma. Nucleic Acids Res. 2012; 40:941-955.
  28. Unraveling the structural complexity in a single-stranded RNA tail: implications for efficient ligand binding in the prequeuosine riboswitch [OA] Catherine D. Eichhorn, Jun Feng, Krishna C. Suddala, Nils G. Walter, Charles L. Brooks, III, and Hashim M. Al-Hashimi. Nucleic Acids Res. 2012; 40:1345-1355.
  29. Identifying G-quadruplex-binding ligands using DNA-functionalized gold nanoparticles. Y Qiao, J Deng, Y Jin, G Chen, & L Wang. Analyst. 2012; 137: 1663.
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• GQ-Structure & Dynamics. Studies aimed at elucidating structure and/or dynamics GQ. This includes experimental techniques such as X-Ray crystallography, NMR, and other spectroscopic methods as well as theoretical approaches such as MD-simulations. [7 articles]

  1. RNA G-Quadruplexes: G-quadruplexes with “U” Turns. Agarwal T, Jayaraj G, Pandey SP, Agarwala P, Maiti S. Curr Pharm Des. 2012 Feb 27. [Epub before print] PMID: 22376111
  2. Formation of pearl-necklace monomorphic G-quadruplexes in the human CEB25 minisatellite. Amrane S, Adrian M, Heddi B, Serero A, Nicolas A, Mergny JL, Phan AT. J Am Chem Soc. 2012 Feb 29. [Epub before print] PMID: 22376028
  3. The Tertiary DNA Structure in the Single-Stranded hTERT Promoter Fragment Unfolds and Refolds by Parallel Pathways via Cooperative or Sequential Events. Yu Z, Gaerig V, Cui Y, Kang H, Gokhale V, Zhao Y, Hurley LH, Mao H. J Am Chem Soc. 2012 Feb 28. [Epub before print] PMID: 22372563
  4. Stability and free energy calculation of LNA modified quadruplex: a molecular dynamics study. AK Chaubey, KD Dubey, and RP Ojha. J Comput Aided Mol Des. 2012. [Epub before print]
  5. Studying the effect of crowding and dehydration on DNA G-quadruplexes. L Petraccone, B Pagano, and C Giancola. Methods. 2012. [Epub before print]
  6. Stability and Structure of Long Intramolecular G-quadruplexes. L Payet and JL Huppert. Biochemistry. 2012. [Epub before print]
  7. The high-resolution crystal structure of a parallel intermolecular DNA G-4 quadruplex/drug complex employing syn glycosyl linkages [OA] GR Clark, PD Pytel, and CJ Squire. Nucleic Acids Res. 2012. [Epub before print]
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• GQ-Supramolecular. Studies related to the design and applications of GQs in supramolecular chemistry. Of particular interest are studies on the use of independent guanosine subunits to guide the self-assembly of complex structures. [o articles]


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This post includes 78 articles divided by categories as follows:

  • GQ-Biology.  13 articles
  • GQ-Methods11 articles
  • GQ-Cations1 article
  • GQ-Nano & Technology. 17 articles
  • GQ-Recognition29 articles
  • GQ-Structure & Dynamics7 articles
  • GQ-Supramolecular0 articles
_____________________________________
[OA] = Open Access


Structural studies of naphthalene diimide ligands with telomeric G-Quadruplex DNA

March 15, 2012 13 comments

Structural Basis for Telomeric G-Quadruplex Targeting by Naphthalene Diimide Ligands

Gavin W. Collie, Rossella Promontorio, Sonja M. Hampel, Marialuisa Micco, Stephen Neidle*, and Gary N. Parkinson*

J. Am. Chem. Soc., 2012, 134 (5), 2723; DOI: 10.1021/ja2102423

A synopsis by Maxier Acosta

Previously Neidle had reported a series on naphthalene diimide (ND) oligo G-quadruplex (OGQ) ligands with side-chains (n) of 3-5 carbons with N-methyl-piperazine end groups. They showed experimentally how it inhibited binding of hPOT1 and topoisomerase IIIα to telomeric DNA and inhibited telomerase activity in MCF7 cells via the stabilization of OGQs (DOI: 10.1016/j.bmcl.2010.09.066). Now, in collaboration with Parkinson, they report the crystalline structure of each one of those naphthalene ligands with the addition of a two-carbons side-chain.

They first give an overview of the tendencies of the overall parallel OGQ (Gtel22) with each ND ligand. With the telomere sequence d(AGGG[TTAGGG]3) they highlight the stacking of two OGQs making a dimer interacting from the 5’ terminal G-quartet. But the ratio between the ND and each OGQ is 1:1. Taking this in consideration, when each ND is bound to the quadruplexes, they force the topology of the loops into parallel strands as first proposed in DOI: 10.1016/j.bmcl.2010.09.066. While going more into detail, stability studies via FRET and inhibition studies where done for each ND. In the case of the ND with a two-carbons side-chain, it didn’t enhanced by much the stability of the Gtel22 due to the inappropriate side-chain length to enable effective interactions (in the OGQ groove) between the protonated N-methyl-piperazine and the DNA backbone phosphates. Although the n=5 ND OGQ complex showed poor quality in its crystal diffraction, it was still higher than that corresponding to n=2. For the n=4 ND, the side-chains were too long to fit well into the grooves as indicated by the disorder of the chains leading to a decrease of strong specific contacts, yet it was still more stabilizing than n=5 ND. For n=3 ND, it was observed that the cation-phosphate interactions were specifically coordinated, making it the best ligand of the small library presented in the paper. The structural features for these ND ligands correlated well with the inhibition of two types of cancer cells (MCF7 and A549).

In the discussion they summarized the data in three major topics: (1) the 1:1 binding of ND and OGQs; (2) the importance of the electrostatic side-chain interaction with the groove; and (3) the retention of the parallel topology of the Gtel22. Also, as might be expected for scientists from a pharmacy school they maintain their focus on how biologically relevant these binders could be for anticancer treatments.

In general, I thought that this was a good OGQ-binder structural article. I know that our systems are difficult to crystallize, yet this type of studies can help us to understand them to a new level so we could also start talking about potential inhibitors among other things. In terms of the organization of the paper, I found confusing the fact that they do not address explicitly some of the figures. In the discussion it was not that clear for me why the NDs induced the parallel topology; so, for that I encourage you guys to read the reference that I mentioned at the beginning, which has additional useful experimental data that may help anyone in the same situation. Other than this, I wish I had seen all of the ND side-chains interactions with the groove (some of them are in the supplementary information).

Raiders of the lost G-quadruplexes …in the human genome

March 14, 2012 15 comments

Small-molecule–induced DNA damage identifies alternative DNA structures in human genes

Raphaël Rodriguez, Kyle M Miller, Josep V Forment, Charles R Bradshaw, Mehran Nikan, Sébastien Britton, Tobias Oelschlaegel, Blerta Xhemalce, Shankar Balasubramanian* & Stephen P. Jackson*

Nature Chemical Biology 8, 301–310 (2012) doi: 10.1038/nchembio.780

A synopsis by Diana Silva Brenes

The authors of this week’s paper play detective to find out -with great detail- what exactly happens to a human cell when it’s treated with the versatile, potent GQ-binder, pyridostatin. Using a combination of biomolecular assays, the authors manage to give strong support for the in vivo formation of GQ-DNA in human cells, and show their role in the activity of the new drug.

Pyridostatin is shown to induce damage to cellular DNA, stumping their proliferation. This happens because cellular checkpoints, which revise DNA before continuing the cellular division cycle, detect the damage and signal to the cell that something is wrong. The cell stops in its tracks to try to correct the problem before it continues the cycle. The drug, however, isn’t too toxic and most cells can survive long-term exposition to it without undergoing apoptosis. Interestingly, inhibition of the checkpoints restores cell proliferation.

Many of the results rely on detecting the presence of γH2AX (a protein that indicates double strand breaks in DNA) as a way to follow damage done to DNA. In cells treated with pyridostatin, γH2AX is present during the DNA transcription and replication processes, pointing at damage to DNA occurring during both stages.

Next, the authors wanted to localize where in the DNA is pyridostatin taking effect. Fluorescence labeling of γH2AX and the telomeres (marked by the labeling of a telomere binding protein) didn’t show co-localization. It was, thus, necessary to modify the drug to add direct fluorescence labeling. Addition of an alkyne group to the drug allowed an in cellulo click reaction with an azide containing fluorescent dye. After making sure that the modified pyridostatin did not affect drug activity, staining of pyridostatin was performed and fluorescent spots (foci) were compared with the a fluorescently labeled human helicase reputed to bind and resolve GQ-DNA during replication. Good co-localization was observed, suggesting that pyridostatin was localized mostly at putative GQ-DNA sites. In another experiment they showed that addition of pyridostatin before of after “freezing” the cellular processes in formaldehyde gave almost identical results, suggesting that GQ structures are pre-folded even without addition of pyridostatin.

They then performed ChIP sequencing to try to figure out which genes (aka, DNA segment) were targeted by pyridostatin. They found several specific genes (mostly away from the telomeres) that sustained pyridostatin induced damage to DNA, and all of them had above average putative GQ sequences. However, not all areas enriched in putative GQ sequences were affected, suggesting that there are other important requirements for interaction.

A particularly affected gene was SRC as confirmed by checking for loss of its corresponding mRNA transcription activity. Out of 25 putative GQ sequences estimated for this gene, 23 of them could be observed to form QGs in vitro using CD and NMR spectra.

The effect of pyridostatin on the bioactivity of SRC was also evaluated. SRC is important for wound healing and motility of cells. Cells treated with pyridostatin displayed a reduced ability to heal. As a control, cells treated with another DNA-damaging drug (DOX), didn’t affect healing, proving that the deficiency was not due merely to DNA damage.

It was previously shown that pyridostatin binds to GQs with enough strength to resist polymerases. It is hypothesized that damage to DNA by pyridostatin is due to mechanical forces breaking the DNA during the cell’s attempt to transcribe or replicate DNA. The findings of this paper support the potential drugability of GQs in cells.

The data reported by this paper is really important for the field of GQ binders and raises large hopes for the future of the field. Being able to use GQ to recognize and regulate specific genes is a dream come true in drug design, and the authors present strong data as to the viability of this approach. As a chemist, it’s difficult to get used to the rather indirect type of evidence that supports these findings, making it hard for me to comment on this paper’s methods. However, the controls and the analyses they did appear to be adequate. Overall, I find the results in this paper to be really important to anyone in the GQ field.

Categories: Lab-blog, Uncategorized Tags: , ,

Battle for supremacy between G-Quadruplex DNA fluorescent probes

March 8, 2012 13 comments

Fluorescence properties of 8-(2-pyridyl)guanine “2PyG” as compared to 2-aminopurine in DNA

Anälle Dumas and Nathan W. Luedtke*

ChemBioChem 2011, 12, 2044–2051; DOI: 10.1002/cbic.201100214

A synopsis by María Del C. Rivera-Sánchez

The motivation of the work reported by Dumas and Luedtke is the development of internal probes for direct readouts of local nucleobases arrangements, dynamics and electronic properties (e.g., electron transfer reactions). Their strategy is based on the incorporation of internal fluorescent probes as energy acceptors in DNA, particularly in hTelo and cKit sequences that fold into oligo-G-quadruplexes (OGQs).

In this article the authors include many of their previously reported data related to 2PyG [Refs 17 and 18] in order to compare its properties with those of 2-aminopurine (2AP), a nucleoside that was not previously evaluated as an internal fluorescent probe for OGQs when directly incorporated into folded G-tetrads. Each publication has different pieces of the puzzle towards understanding the importance of 2PyG as a plausible fluorescent probe and how it compares with other potential probes like 2AP. Thus, from those “scattered” pieces of information the picture that emerges can be summarized in the synthesis of a small family of 8-substituted-2’-deoxyguanosine analogues (2PyG, 4PVG and STG) and the evaluation of their photophysical properties in CH3CN and H2O. The cool part is that the phosphoramidite versions of these analogues were synthesized and the nucleosides incorporated into strategic positions of hTelo and cKit OGQs. The impact on the global structure and stability of hTeloG9, hTelo17, hTeloG23, cKitG10 or cKit15 having 8-substituted analogues, 2AP or thymine directly incorporated into folded G-tetrads, was evaluated by means of circular dichroism (CD) and CD-melting assays. Experiments using the afore mentioned ss OGQs were done in K+-, Na+-, and Li+-buffer and were compared to data from ds hTeloG9, ds hTeloG17, ds hTeloG23, and ds cKitG15 in Na+-buffer. In addition, the proficiency of analogues like 2PyG, 2AP and thymine as internal fluorescence probes was assed by measuring the quantum yield (Φ) and energy-transfer efficiency (ηT) of the substituted-duplex and ss-OGQs.

The data gathered from these experiments points to 2PyG as an outstanding internal fluorescent probe due to its higher quantum yield (Φ), once incorporated into folded oligonucleotides (Φ = 0.03–0.15) versus the free nucleoside in water (Φ =0.02), when compared to all other nucleosides evaluated. In addition, when exciting at 260 nm, the energy-transfer efficiencies from unmodified bases to 2PyG are 4–10-fold higher in ss-OGQs than in the corresponding duplex DNA. This energy-transfer process is favored by the O6 ion coordination within the central channel of G-tetrads and is distinctive of GQ structures (not duplex DNA). When this phenomena is combined with the high molar absorptivity of DNA it results in fluorescence enhancements of 10–30-fold for 2PyG-containing OGQs versus the corresponding ss- or ds-DNA. This highlights the potential of using 2PyG as a fluorescent probe for the detection of OGQ formation at lower concentrations among other applications. Unfortunately, the Φ or ηT of 2AP-containing DNAs are much lower than those for 2PyG-containing DNAs.

The ideal internal fluorescent probe should have very little effect on the global structure of the system evaluated. Particularly, the effect of 2PyG incorporation within folded G-tetrads seems to be context dependent. For example, 2PyG have little impact on the global structure and positive stability of hTeloG9 in K+- or Na+-buffer do to the syn conformational preference shared by this position and 2PyG. However, even though G15 in cKit (wt) have an anti conformational preference, CD spectra suggest that the incorporation of 2PyG have little impact on the global structure, but caused a small decreased in the Tm of cKitG15. On the contrary, the incorporation of 2PyG at hTeloG23 (in K+ or Na+-buffer) just allows the formation of an OGQ structure where G23 is in a syn conformation that is mainly observed on Na+-buffer. As a general trend, considering all the data discuss in the article, we can say that base stacking and pairing interactions can sometimes overcome the energy barrier of a preferred glycosidic bond conformation stabilizing the resulting OGQ or ds-DNA structure. Still, 2PyG has to be strategically located within OGQs to minimize detrimental effects, although, similar substitutions with 2AP or thymine are much more significant. Regarding 2AP, a priori I would not consider it a good mimic of guanine when positioned directly into folded G-tetrads because it lacks a carbonyl at the C6 and the N1-H, which prevents the formation of at least three interactions essential for an effective participation in the formation of a G-tetrad. Therefore, I consider that the comparison of 2PyG against other 8-substitutted nucleobases as they did on ref. 18 is more appropriate than comparing it against 2AP. The system reported by Dumas and Luedtke might have applications on fundamental studies related to ODNs and/or OQGs dynamics and their electronic properties, but I don’t picture them into practical, biophysical or technological applications.

This was a nice article in which it the authors combined many previous results with new complementary data provides a better understanding of the true potential and limitations of 2PyG as an internal fluorescent probe. They also evaluated for the detrimental effect induced by 2AP when incorporated into folded G-tetrads. The experiments reported included the appropriate controls like those done using thymine-containing sequences. In addition, their experimental section includes appropriate details such as the preparation of the DNA samples used.

Structural elucidation of dimeric DNA G-quadruplexes

February 1, 2012 13 comments

Stacking of G-quadruplexes: NMR structure of a G-rich oligonucleotide with potential anti-HIV and anticancer activity

Ngoc Quang Do, Kah Wai Lim, Ming Hoon Teo, Brahim Heddi1 and Anh Tuan Phan

Nucleic Acids Research, 2011, Vol. 39, No. 21, 9448–9457, doi:10.1093/nar/gkr539

A synopsis by Marilyn García-Arriaga

In order to gain better understanding of the nature of this structures, Phan and colleagues reported the structural analysis of a dimeric OGQ with the sequence (GGGT)4 (T30695) in K+ solution. This dimer is composed of two identical propeller-type parallel-stranded OGQ subunits each containing three tetrads that are stacked via the 5’-5’ interface. NMR structural studies of the OGQ formed by T30695 and T40214 ((GGGC)4), in K+ solution, share similar 1D and 2D NOESY spectral features. Furthermore, preliminary CD studies show the positive band at 260 nm characteristic of a parallel-stranded OGQ, in contrast to a previous report. In order to perform a detailed structural analysis by NMR an accurate assignment of the signals is essential. This task is more challenging in systems of high symmetry, thus, to overcome this problem they prepared a T30695 analogue with a single guanine-to-inosine substitution, GIGT(GGGT)3 (). This modification greatly improves the NMR spectra of the assembly allowing the assignment of the signals without ambiguity. Not only does this derivative show the same structural characteristics in the 1D and 2D NOESY spectra, but it also show similar positive band in the CD spectra and pattern in the gel electrophoresis experiments. 15N-labeling of the guanine imino protons and other protons of J19 enabled establishing the correlations in the COSY, TOCSY HSQC and NOESY spectra. In contrast to what was previously reported, the moderate intensity of the intra-residue H8/H6-H10 NOEs suggest that all residues adopt anti glycosidic bond conformation. The combined evidence suggested that the resulting structure is a propeller-type parallel-stranded OGQ with a three-tetrad core and three double-chain-reversal loops.

Evidence of the 5’-end stacking to form the dimer was obtained from gel electrophoresis in which the migration rate of J19 was similar to that of 93del, an interlocked dimeric OGQ. In addition, the migration rate of J19 was slower than that of a monomeric propeller-type OGQ. Furthermore, solvent-exchange experiments reveal that the imino protons of guanines in the outer tetrads (5’-end) are protected from exchange with D2O. Also, additions of bases in the 5’-end of J19 disrupt the dimer formation. The solution structure of J19 was generated after distance-restrained molecular dynamics refinement in this structure the core of the quadruplex show a close packing across the interfaces of the tetrads. Also, the directionality of the hydrogen bonds was the same for each subunit and opposite between the two structures in the dimer. The thymine bases are projected outwards in a double-chain-reversal loop. In more details, the sugars from the two end-tetrads are contiguous to one another and the backbones of the two dimer subunits are aligned in a staggered mode, maximizing the overlap of the five and six membered rings on the interface. They were able to conclude this by the identification of NOEs correlations among the base and the sugar protons of the end tetrads.

Finally, in order to assess if those OGQs conserved anti-HIV activity, they performed a reverse ‘disintegration’ reaction assay using T30695, J19 and their derivatives. They concluded that the derivatives containing thymines at the 5’-end were less active, which can be attributed to the lost of their ability to form stacked dimeric structures.

Once again Phan and colleagues present an impressive amount of work, but most of all, an incredible level of analysis. At the experimental level, the work is well supported and all the proper control experiments were performed. In contrast, the narrative and presentation of the data was least successful, in my opinion, it lacks details in the arguments of some conclusions.