GQW articles: April 2012 edition

This post includes 43 articles divided by category as follows:

  • GQ-Biology (GQB).  9 articles
  • GQ-Methods (GQM). 6 articles
  • GQ-Cations (GQC). 0 articles
  • GQ-Nano & Technology (GQNT). 9 articles
  • GQ-Recognition (GQR). 10 articles
  • GQ-Structure & Dynamics (GQSD). 8 articles
  • GQ-Supramolecular (GQS). 1 article
April wasn’t as busy a month as March, where I listed 78 articles (!) for the month, but it was the second busiest month of this year in terms of publications related to GQs. The distribution of articles for April is more or less even, with the exception of the GQC and GQS, with a grand total of just one paper. This contrasts the the distribution of articles for March where the GQNT and GQR categories comprised more than half of all publications in the list. I haven’t classified (although I hope to do so soon…) the articles from January and February, but just to put in perspective how ‘busy’ March was, in those two months I listed 21 and 14 articles, respectively. So, I better stop writing and continue reading because I have a lot of catching up to do.
_____________________________________
• 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) [9 articles]

  1. The human RecQ helicases BLM and RECQL4 cooperate to preserve genome stability. Dharmendra Kumar Singh, Venkateswarlu Popuri, Tomasz Kulikowicz, Igor Shevelev, Avik K. Ghosh, Mahesh Ramamoorthy, Marie L. Rossi, Pavel Janscak, Deborah L. Croteau, & Vilhelm A. Bohr; Nucleic Acids Res. 28 April 2012 [Epub before print]
  2. Replication Protein A Unfolds G-Quadruplex Structures with a Varying Degree of Efficiency. Qureshi MH, Ray S, Sewell AL, Basu S, Balci H. J Phys Chem B. 2012 Apr 14. [Epub ahead of print] PMID: 22500657
  3.  G-quadruplexes in RNA biology; Millevoi S, Moine H, Vagner S. Wiley Interdiscip Rev RNA. 2012 Apr 4. doi: 10.1002/wrna.1113. [Epub before print] PMID: 22488917
  4. Searching for Non-B DNA-Forming Motifs Using nBMST (Non-B DNA Motif Search Tool). Cer RZ, Bruce KH, Donohue DE, Temiz NA, Mudunuri US, Yi M, Volfovsky N, Bacolla A, Luke BT, Collins JR, Stephens RM. Curr Protoc Hum Genet. 2012 Apr; Chapter 18:Unit18.7. PMID: 22470144
  5. Human telomeres replicate using chromosome-specific, rather than universal, replication programs. WC Drosopoulos, ST Kosiyatrakul, Z Yan, SG Calderano, & CL Schildkraut. J Cell Biol. 2012; 197: 253.
  6. Telomere maintenance mechanisms in malignant peripheral nerve sheath tumors: expression and prognostic relevance. L Venturini, MG Daidone, R Motta, G Cimino-Reale, SF Hoare, A Gronchi, M Folini, WN Keith, and N Zaffaroni; Neuro Oncol. 2012. [Epub before print]
  7. Functional binding of hexanucleotides to 3C protease of hepatitis A virus. Bärbel S. Blaum, Winfried Wünsche, Andrew J. Benie, Yuri Kusov, Hannelore Peters, Verena Gauss-Müller, Thomas Peters, and Georg Sczakiel. Nucleic Acids Res. 2012; 40:3042-3055.
  8. Overcoming natural replication barriers: differential helicase requirements. Ranjith P. Anand, Kartik A. Shah, Hengyao Niu, Patrick Sung, Sergei M. Mirkin, & Catherine H. Freudenreich. Nucleic Acids Res. 2012 Feb; 40 (3):1091-1105. Epub 2011 Oct 7.
  9. The orientation of the C-terminal domain of the Saccharomyces cerevisiae Rap1 protein is determined by its binding to DNA. Béatrice Matot, Yann-Vaï Le Bihan, Rachel Lescasse, Javier Pérez, Simona Miron, Gabriel David, Bertrand Castaing, Patrick Weber, Bertrand Raynal, Sophie Zinn-Justin, Sylvaine Gasparini, and Marie-Hélène Le Du. Nucleic Acids Res. 2012; 40:3197-3207.
_____________________________________
• GQ-Methods. Application and development of methods and techniques to study GQs. [6 articles]

  1. Isothermal folding of G-quadruplexes. Gray RD, Chaires JB. Methods. 2012 Apr 16. [Epub ahead of print] PMID: 22525787
  2. Single-molecule investigation of G-quadruplex using a nanopore sensor. Shim J, Gu LQ. Methods. 2012 Apr 2. [Epub before print]  PMID: 22487183
  3. Normalized Affymetrix expression data are biased by G-quadruplex formation. Hugh P. Shanahan, Farhat N. Memon, Graham J. G. Upton, & Andrew P. Harrison. Nucleic Acids Res. 2012; 40:3307-3315.
  4. High-resolution 39K NMR spectroscopy of bio-organic solids. Wu G, Gan Z, Kwan IC, Fettinger JC, Davis JT. J Am Chem Soc. 2011 Dec 14;133(49):19570-3. Epub 2011 Aug 12. PMID: 21819148
  5. Mass spectrometry and ion mobility spectrometry of G-quadruplexes. A study of solvent effects on dimer formation and structural transitions in the telomeric DNA sequence d(TAGGGTTAGGGT). R Ferreira, A Marchand, & V Gabelica. Methods. 2012. [Epub before print] PMID: 22465284
  6. Molecular dynamics simulations of G-DNA and perspectives on the simulation of nucleic acid structures. J Sponer, X Cang, and TE Cheatham 3rd. Methods. 2012. [Epub before print] PMID: 22525788
_____________________________________
• GQ-Nano & Technology. The design and development of GQ-based nanostructures. The use of GQs as components in devices (e.g., sensors). [9 articles]

  1. Fluorescence Detection of DNA, Adenosine-5′-Triphosphate (ATP) and Telomerase Activity by Zn(II)-Protoporphyrin IX/G-Quadruplex Labels. Zhang Z, Sharon E, Freeman R, Liu X, Willner I. Anal Chem. 2012 Apr 29. [Epub before print]  PMID: 22540661
  2. Label-Free Ultrasensitive Detection of Human Telomerase Activity Using Porphyrin-Functionalized Graphene and Electrochemiluminescence Technique. Wu L, Wang J, Feng L, Ren J, Wei W, Qu X. Adv Mater. 2012 Apr 10. doi: 10.1002/adma.201200412. [Epub before print] PMID: 22488983
  3. A simple, post-additional antioxidant capacity assay using adenosine triphosphate-stabilized 2,2′-azinobis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) radical cation in a G-quadruplex DNAzyme catalyzed ABTS-H(2)O(2) system. Jia SM, Liu XF, Kong DM, Shen HX. Biosens Bioelectron. 2012 Mar 23. [Epub ahead of print] PMID: 22487010
  4. Colorimetric detection of cholesterol with G-quadruplex-based DNAzymes and ABTS(2-). Li R, Xiong C, Xiao Z, Ling L. Anal Chim Acta. 2012 Apr 29;724:80-5. Epub 2012 Feb 27. PMID: 22483213
  5. DNA origami as biocompatible surface to match single-molecule and ensemble experiments. Andreas Gietl, Phil Holzmeister, Dina Grohmann, & Philip Tinnefeld. Nucleic Acids Res. published 20 April 2012, 10.1093/nar/gks326
  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. 2012; 40:e56.
  7.  DNA origami as biocompatible surface to match single-molecule and ensemble experiments. Andreas Gietl, Phil Holzmeister, Dina Grohmann, & Philip Tinnefeld. Nucleic Acids Res. published 20 April 2012. [Epub before print]
  8. Hemin/G-quadruplex simultaneously acts as NADH oxidase and HRP-mimicking DNAzyme for simple, sensitive pseudobienzyme electrochemical detection of thrombin. Y Yuan, R Yuan, Y Chai, Y Zhuo, X Ye, X Gan, & L Bai. Chem Commun. 2012. [Epub before print]
  9. DNAzyme-based turn-on chemiluminescence assays in homogenous media. M Zhou, Y Liu, Y Tu, G Tao, and J Yan Biosens Bioelectron. 2012. [Epub before print] PMID: 22465444
_____________________________________
• GQ-Recognition. Discovery and development of (mostly) small molecule ligands that recognize GQs (synthesis; design; pharmacology; medicinal chemistry). [10 articles]

  1. Recent Progress and Future Potential for Metal Complexes as Anticancer Drugs Targeting G-quadruplex DNA. Zhang J, Zhang F, Li H, Liu C, Xia J, Ma L, Chu W, Zhang Z, Chen C, Li S, Wang S. Curr Med Chem. 2012 Apr 20. [Epub ahead of print] PMID: 22519400
  2. 12-N-Methylated 5,6-dihydrobenzo[c]acridine derivatives: A new class of highly selective ligands for c-myc G-quadruplex DNA. Liao SR, Zhou CX, Wu WB, Ou TM, Tan JH, Li D, Gu LQ, Huang ZS. Eur J Med Chem. 2012 Mar 30. [Epub before print] PMID: 22513122
  3. Induction of senescence in cancer cells by a G-quadruplex stabilizer BMVC4 is independent of its telomerase inhibitory activity. Huang FC, Chang CC, Wang JM, Chang TC, Lin JJ. Br J Pharmacol. 2012 Apr 18. doi: 10.1111/j.1476-5381.2012.01997.x. [Epub before print] PMID: 22509942
  4. d(TGGGAG) with 5′-nucleobase-attached large hydrophobic groups as potent inhibitors for HIV-1 envelop proteins mediated cell-cell fusion. Chen W, Xu L, Cai L, Zheng B, Wang K, He J, Liu K. Bioorg Med Chem Lett. 2011 Oct 1;21(19):5762-5764. Epub 2011 Aug 8. PMID: 21873060
  5. Spectroscopic, molecular modeling and NMR-spectroscopic investigation of the binding mode of the natural alkaloids berberine and sanguinarine to human telomeric G-quadruplex DNA. Bessi I, Bazzicalupi C, Richter C, Jonker HR, Saxena K, Sissi C, Chioccioli M, Bianco S, Bilia AR, Schwalbe H, Gratteri P. ACS Chem Biol. 2012 Apr 9. [Epub before print]  PMID: 22486369
  6. Disubstituted 1,8-dipyrazolcarbazole derivatives as a new type of c-myc G-quadruplex binding ligands. Chen WJ, Zhou CX, Yao PF, Wang XX, Tan JH, Li D, Ou TM, Gu LQ, Huang ZS. Bioorg Med Chem. 2012 Mar 21. [Epub before print] PMID: 22484007
  7. The impact of the G-quadruplex conformation in the development of novel therapeutic and diagnostic agents. Alcaro S. Curr Pharm Des. 2012 May 1;18(14):1865-6. PMID: 22471996
  8. The Interaction of Telomeric DNA and C-myc22 G-Quadruplex with 11 Natural Alkaloids. Ji X, Sun H, Zhou H, Xiang J, Tang Y, Zhao C. Nucleic Acid Ther. 2012 Apr;22(2):127-36. PMID: 22480315
  9. Water soluble extended naphthalene diimides as pH fluorescent sensors and G-quadruplex ligands. Doria F, Nadai M, Sattin G, Pasotti L, Richter SN, Freccero M. Org Biomol Chem. 2012 Apr 3. [Epub before print] PMID: 22469919
  10. Structure of Musashi1 in a complex with target RNA: the role of aromatic stacking interactions. Takako Ohyama, Takashi Nagata, Kengo Tsuda, Naohiro Kobayashi, Takao Imai, Hideyuki Okano, Toshio Yamazaki, and Masato Katahira. Nucleic Acids Res. 2012; 40:3218-3231.
_____________________________________
• 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. [8 articles]

  1. Towards characterization of DNA structure under physiological conditions in vivo at the single-molecule level using single-pair FRET. Tomás Fessl, Frantisek Adamec, Tomás Polívka, Silvie Foldynová-Trantírková, Frantisek Vácha, & Lukás Trantírek. Nucleic Acids Res. 28 April 2012 [Epub before print]
  2. 8-Oxo-7,8-dihydrodeoxyadenosine: The first example of a native DNA lesion that stabilizes human telomeric G-quadruplex DNA. Aggrawal M, Joo H, Liu W, Tsai J, Xue L. Biochem Biophys Res Commun. 2012 Apr 19. [Epub before print] PMID: 22538366
  3. Time-resolved NMR spectroscopic studies of DNA i-motif folding reveal kinetic partitioning. Lieblein AL, Buck J, Schlepckow K, Fürtig B, Schwalbe H. Angew Chem Int Ed Engl. 2012 Jan 2; 51 (1):250-253. doi: 10.1002/anie.201104938. PMID: 22095623
  4. The Guanine Bases in DNA G-Quadruplex Adopt Non-Planar Geometries Owing to Solvation and Base Pairing. Sychrovsky V, Sochorová Vokáčová Z, Trantirek L. J Phys Chem A. 2012 Apr 3. [Epub before print] PMID: 22471881
  5. Conformations of individual quadruplex units studied in the context of extended human telomeric DNA. Singh V, Azarkh M, Drescher M, Hartig JS. Chem Commun. 2012 Apr 24. [Epub before print]  PMID: 22531827
  6. Molecular dynamics studies of the STAT3 homodimer:DNA complex: relationships between STAT3 mutations and protein-DNA recognition. J Husby, AK Todd, SM Haider, G Zinzella, DE Thurston, and S Neidle. J Chem Inf Model. 2012. [Epub before print]
  7. Replication Protein A Unfolds G-Quadruplex Structures with a Varying Degree of Efficiency. MH Qureshi, S Ray, AL Sewell, S Basu, and H Balci. J Phys Chem B. 2012. [Epub before print]
  8. Solution-state structure of an intramolecular G-quadruplex with propeller, diagonal and edgewise loops. Maja Marusic, Primoz Sket, Lubos Bauer, Viktor Viglasky, & Janez Plavec. Nucleic Acids Res. 24 April 2012. [Epub before print] PMID: 22532609
_____________________________________
• GQ-Supramolecular. Studies related to the design and applications of GQs in supramolecular chemistry. (assemblies; molecular devices) [1 article]

  1. Molecular “light switch” for G-quadruplex DNA: cycling the switch on and off. Shi S, Zhao J, Gao X, Lv C, Yang L, Hao J, Huang H, Yao J, Sun W, Yao T, Ji L. Dalton Trans. 2012 Apr 10. [Epub before print] PMID: 22488166
_____________________________________
Advertisements

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)

_____________________________________

• 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.
_____________________________________
• 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
_____________________________________
• 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
_____________________________________
• 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
_____________________________________
• 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.
_____________________________________
• 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]
_____________________________________
• 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]


_____________________________________

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


GQW articles: February 2012 edition

April 12, 2012 1 comment

Image
Following is a list of articles related to G-quadruplex research published (for the first time on the web or “officially” in print) during the month of February 2012. This post includes 14 articles divided by category as follows:

  • GQ-Biology (GQB).  6 articles
  • GQ-Cations (GQC). 1 articles
  • GQ-Methods (GQM). 1 articles
  • GQ-Nano & Technology (GQNT). 3 articles
  • GQ-Recognition (GQR). 2 articles
  • GQ-Structure & Dynamics (GQSD). 1 articles
  • GQ-Supramolecular (GQS). 0 article
_____________________________________

• 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) [6 articles]

  1. Charge and substituent effects on the stability of porphyrin/G-quadruplex adducts. Ramos CI, Tomé JP, Santana-Marques MG. J Mass Spectrom. 2012 Feb;47(2):173-179. doi: 10.1002/jms.2048. PMID: 22359326
  2. Self-entanglement of long linear DNA vectors using transient non-B-DNA attachment points: A new concept for improvement of non-viral therapeutic gene delivery. Tolmachov OE. Med Hypotheses. 2012 Feb 20. [Epub before print] PMID: 22356834
  3.  5′-UTR RNA G-quadruplexes: translation regulation and targeting. [OA] Bugaut A, Balasubramanian S. Nucleic Acids Res. 2012 Feb 20. [Epub before print] PMID: 22351747
  4. A telomerase-associated RecQ protein-like helicase resolves telomeric G-quadruplex structures during replication. Postberg J, Tsytlonok M, Sparvoli D, Rhodes D, Lipps HJ. Gene. 2012 Feb 2. [Epub before print] PMID: 22327026
  5. New insights into replication origin characteristics in metazoans. [OA] Cayrou C, Coulombe P, Puy A, Rialle S, Kaplan N, Segal E, Méchali M. Cell Cycle. 2012 Feb 15; 11 (4). PMID: 22307000
  6. A G-Rich Element Forms a G-Quadruplex and Regulates Bace1 mRNA Alternative Splicing. Fisette JF, Montagna DR, Mihailescu MR, Wolfe MS. J Neurochem. 2012 Feb 3. [Epub before print] doi: 10.1111/j.1471-4159.2012.07680.x. PMID: 22303960
_____________________________________
• GQ-Cations. Studies aimed at elucidating the role of cations in GQ structure and/or dynamics. [1 articles]

  1. Cation binding to 15-TBA quadruplex DNA is a multiple-pathway cation-dependent process. [OA] Reshetnikov RV, Sponer J, Rassokhina OI, Kopylov AM, Tsvetkov PO, Makarov AA, Golovin AV. Nucleic Acids Res. 2011 Dec;39 (22):9789-9802. Epub 2011 Sep 5. PMID: 21893589
_____________________________________
• GQ-Methods. Application and development of methods and techniques to study GQs. [1 articles]

  1.  Experimental approaches to identify cellular G-quadruplex structures and functions. Antonio MD, Rodriguez R, Balasubramanian S. Methods. 2012 Feb 11. [Epub before print] PMID: 22343041
_____________________________________
• GQ-Nano & Technology. The design and development of GQ-based nanostructures. The use of GQs as components in devices (e.g., sensors). [3 articles]

  1. Following Glucose Oxidase Activity by Chemiluminescence and Chemiluminescence Resonance Energy Transfer (CRET) Processes Involving Enzyme-DNAzyme Conjugates. [OA] Niazov A, Freeman R, Girsh J, Willner I. Sensors. 2011;11(11):10388-97. Epub 2011 Oct 31. PMID: 22346648
  2. A label-free G-quadruplex-based switch-on fluorescence assay for the selective detection of ATP. He HZ, Pui-Yan Ma V, Leung KH, Shiu-Hin Chan D, Yang H, Cheng Z, Leung CH, Ma DL. Analyst. 2012 Feb 20. [Epub before print] PMID: 22343772
  3. A novel biosensing strategy for screening G-quadruplex ligands based on graphene oxide sheets. Wang H, Chen T, Wu S, Chu X, Yu R. Biosens Bioelectron. 2012 Jan 26. [Epub before print] PMID: 22336439
_____________________________________
• GQ-Recognition. Discovery and development of (mostly) small molecule ligands that recognize GQs (synthesis; design; pharmacology; medicinal chemistry). [2 articles]

  1. Small-molecule-induced DNA damage identifies alternative DNA structures in human genes. Rodriguez R, Miller KM, Forment JV, Bradshaw CR, Nikan M, Britton S, Oelschlaegel T, Xhemalce B, Balasubramanian S, Jackson SP. Nat Chem Biol. 2012 Feb 5. doi: 10.1038/nchembio.780 [Epub before print] PMID: 22306580
  2.  Alternative DNA structures: G4 DNA in cells: itae missa est? Jean-Louis Mergny. Nature Chemical Biology 8, 225–226 (2012) doi:10.1038/nchembio.793 Published online 15 February 2012
_____________________________________
• 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. [1 articles]

  1.  Unique structural features of interconverting monomeric and dimeric G-quadruplexes adopted by a sequence from intron of N-myc gene. Trajkovski M, Webba da Silva M, Plavec J. J Am Chem Soc. 2012 Feb 3. [Epub before print] PMID: 22303871
_____________________________________
• GQ-Supramolecular. Studies related to the design and applications of GQs in supramolecular chemistry. (assemblies; molecular devices) [0 articles]

_____________________________________
[OA] = Open Access
Categories: List of articles

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.

GQW articles: January 2012 edition

February 16, 2012 1 comment

Image

Following is a (non-comprehensive) list of articles related to G-quadruplex research published (for the first time on the web or “officially” in print) during the month of January 2012. This post includes 21 articles divided by category as follows:

  • GQ-Biology (GQB).  4 articles
  • GQ-Cations (GQC). 3 articles
  • GQ-Methods (GQM). 1 articles
  • GQ-Nano & Technology (GQNT). 7 articles
  • GQ-Recognition (GQR). 4 articles
  • GQ-Structure & Dynamics (GQSD). 2 articles
  • GQ-Supramolecular (GQS). 0 article
_____________________________________

• 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) [4 articles]

  1. Tools for Investigation of the RNA Endonuclease Activity of Mammalian Argonaute2 Protein. Yang N, Cao Y, Han P, Zhu X, Sun L, Li G. Anal Chem. 2012 Jan 26. [Epub before print] PMID: 22283827
  2. Telomestatin impairs glioma stem cell survival and growth through the disruption of telomeric G-quadruplex and inhibition of the proto-oncogene, c-Myb. Miyazaki T, Pan Y, Joshi K, Purohit D, Hu B, Demir H, Mazumder S, Okabe S, Yamori T, Viapiano MS, Shin-Ya K, Seimiya H, Nakano I. Clin Cancer Res. 2012 Jan 9. [Epub before print] PMID: 22230766
  3. Structure of noncoding RNA is a determinant of function of RNA binding proteins in transcriptional regulation [OA] Oyoshi T, Kurokawa R. Cell Biosci. 2012 Jan 3;2 (1):1. PMID: 22214309
  4. Potential G-quadruplexes in the human long non-coding transcriptome. Jayaraj GG, Pandey S, Scaria V, Maiti S. RNA Biol. 2012 Jan 1; 9 (1). PMID: 22258148
_____________________________________
• GQ-Cations. Studies aimed at elucidating the role of cations in GQ structure and/or dynamics. [3 articles]

  1.  G-Quadruplexes and Metal Ions. Campbell NH, Neidle S. Met Ions Life Sci. 2012;10: 119-134. PMID: 22210337
  2. Free-Energy Landscapes of Ion Movement through a G-Quadruplex DNA Channel. Akhshi P, Mosey NJ, Wu G. Angew Chem Int Ed Engl. 2012 Jan 13. doi: 10.1002/anie.201107700. PMID: 22241618
  3. Kinetics and mechanism of G-quadruplex formation and conformational switch in a G-quadruplex of PS2.M induced by Pb2+ [OA] Liu W, Zhu H, Zheng B, Cheng S, Fu Y, Li W, Lau TC, Liang H. Nucleic Acids Res. 2012 Jan 12. [Epub before print] PMID: 22241774
_____________________________________
• GQ-Methods. Application and development of methods and techniques to study GQs. [1 articles]

  1. G-quadruplex structure and stability illuminated by 2-aminopurine phasor plots [OA] Buscaglia R, Jameson DM, Chaires JB. Nucleic Acids Res. 2012 Jan 12. [Epub before print] PMID: 22241767
_____________________________________
• GQ-Nano & Technology. The design and development of GQ-based nanostructures. The use of GQs as components in devices (e.g., sensors). [7 articles]

  1. Input-Dependent Induction of Oligonucleotide Structural Motifs for Performing Molecular Logic. [OA] Li T, Ackermann D, Hall AM, Famulok M. J Am Chem Soc. 2012 Jan 31. PMID: 22296341
  2. A novel label-free fluorescent sensor for the detection of potassium ion based on DNAzyme. Fan X, Li H, Zhao J, Lin F, Zhang L, Zhang Y, Yao S. Talanta. 2012 Jan 30;89:57-62. PMID: 22284459
  3. DNA G-quadruplex-templated formation of the fluorescent silver nanocluster and its application to bioimaging. Ai J, Guo W, Li B, Li T, Li D, Wang E. Talanta. 2012 Jan 15;88:450-455. PMID: 22265525
  4. Cationic Conjugated Polyelectrolytes-Triggered Conformational Change of Molecular Beacon Aptamer for Highly Sensitive and Selective Potassium Ion Detection. Kim B, Jung IH, Kang M, Shim HK, Woo HY. J Am Chem Soc. 2012 Jan 14. [Epub before print] PMID: 22280349
  5. Growth Mechanisms of Fluorescent Silver Clusters Regulated by Polymorphic DNA templates: A DFT Study. Wu J, Fu Y, He Z, Han Y, Zheng L, Zhang J, Li W. J Phys Chem B. 2012 Jan 13. PMID: 22242908
  6. G-Quadruplex-Forming Oligonucleotide Conjugated to Magnetic Nanoparticles: Synthesis, Characterization and Enzymatic Stability Assays. Musumeci D, Oliviero G, Roviello GN, Bucci EM, Piccialli G. Bioconjug Chem. 2012 Jan 12. [Epub before print] PMID: 22239558
  7. Studies of the Activity of Peroxidase-Like DNAzyme by Modifying 3′- or 5′-End of Aptamers. Zhang M, Li H, Deng M, Weng X, Ma H, Feng S, Zhou Y, Zhou X. Chem Biodivers. 2012 Jan; 9 (1):170-180. doi: 10.1002/cbdv.201100040. PMID: 22253114
_____________________________________
• GQ-Recognition. Discovery and development of (mostly) small molecule ligands that recognize GQs (synthesis; design; pharmacology; medicinal chemistry). [4 articles]

  1.  The porphyrin TmPyP4 unfolds the extremely stable G-quadruplex in MT3-MMP mRNA and alleviates its repressive effect to enhance translation in eukaryotic cells. [OA] Morris MJ, Wingate KL, Silwal J, Leeper TC, Basu S. Nucleic Acids Res. 2012 Jan 20. [Epub before print] PMID: 22266651
  2. Structural basis for telomeric G-quadruplex targeting by naphthalene diimide ligands. Collie GW, Promontorio R, Hampel SM, Micco M, Neidle S, Parkinson GN. J Am Chem Soc. 2012 Jan 12. [Epub before print] PMID: 22280460
  3. Synthesis and human telomeric G-quadruplex DNA-binding activity of glucosaminosides of shikonin/alkannin. He H, Bai LP, Jiang ZH. Bioorg Med Chem Lett. 2012 Jan 10. [Epub before print] PMID: 22281188
  4. Recognize three different human telomeric G-quadruplex conformations by quinacrine. Sun H, Xiang J, Li Q, Liu Y, Li L, Shang Q, Xu G, Tang Y. Analyst. 2012 Jan 5. [Epub before print] PMID: 22223064
_____________________________________
• 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. [2 articles]

  1. Crystal structure of a c-kit promoter quadruplex reveals the structural role of metal ions and water molecules in maintaining loop conformation. [OA] Dengguo Wei, Gary N. Parkinson, Anthony P. Reszka, and Stephen Neidle. 28 January 2012. [Epub before print]
  2. G-Qadruplexes from Human Telomeric DNA: How Many Conformations in PEG Containing Solutions? Petraccone L, Malafronte A, Amato J, Giancola C. J Phys Chem B. 2012. Jan 23. [Epub before print] PMID: 22268560
_____________________________________
• GQ-Supramolecular. Studies related to the design and applications of GQs in supramolecular chemistry. (assemblies; molecular devices) [0 articles]

_____________________________________
[OA] = Open Access