Archive for February, 2012

GQW articles: January 2012 edition

February 16, 2012 1 comment


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

Energetics of cations moving within G-Quadruplex DNA

February 8, 2012 14 comments
Parisa Akhshi, Nicholas J. Mosey, Gang Wu*
Angew Chem Int Ed Engl. 2012 Jan 13. doi: 10.1002/anie.201107700.
PMID: 22241618
A synopsis by Mariana Martín-Hidalgo

Gang Wu and coworkers are presenting in this short communication a molecular dynamic simulation to elucidate the free-energy landscape for the movement of three monovalent cations (Na+, K+, NH4+)through the central channel of a tetramolecular oligo G-quadruplex (OGQ).  The importance of this work strikes in the potential use of OGQs as synthetic ion channels, an application that has been considered by a number of research groups in last decade.

To perform this study they divided the ion movement in two regions: inside the OGQ and at the entrance/exit region.  They found that for the inner OGQ region, Na+ showed a lower energy barrier (4-5 kcal/mol) when compared to K+ and NH4+ (13-15 kcal/mol).  They made reference to experimental data to backup these computational results, plus they argue that the ionic radii differences between them are responsible for the observed energy barriers.  K+ and NH4+ have similar ionic radii (1.51 and 1.66 Å for octahedral coordinate ions respectively) while Na+ (1.18 Å) being a little bit smaller can diffuse through the tetrads easily.

They also highlighted the possibility of having what they refer to as “leaks” through the tetrad (sideway movement of ions) instead of the proposed continuous ion movement through the central channel.  They basically found that the energy barrier for that ion movement is too high (50-60 kcal/mol) to make it possible, discarding this possibility. I have to bring an issue related to their expression in this paragraph (second page, first paragraph), because they mentioned and I cite: “ there has never been experimental proof that ions would not “leak” out from the side wall of the G-quadruplex channel”.  I know the authors are emphasizing in the study of ion movement for OGQ’s but we know that there are OGQs and supramolecular GQs (SGQs) self-assembled from a variety of guanine derivatives. So, in my view they should’ve specified that lateral ion movement haven’t been shown for OGQs (perhaps in a note), but it had for SGQs. Specifically, in 2006 the Davis group reported (JACS 128 (47), 15269) the first evidence of “sideway” displacement for cations in a four-tetrad (4T) SGQ (i.e. a hexadecamer formed from the dimerization of two octamers). The mechanism of exchange of course would be different in a 4T-SGQ like Davis’ when compared to Wu’s 4T-OGQ and we can discuss those on Fridays presentation.

In the second region, the entrance/exit sides, the energy barrier encountered for K+ and NH4+ was 20 kcal/mol, while for Na+ was 14 kcal/mol, both values correlate well with the experimental data reported in the literature. Another important point of discussion the hydration states of these cations.  The inner cations are fully dehydrated while the ones located at the entrance/exit positions might be hydrated because of the transition to/from the bulk media.

From my point of view the most important part of this report is their comparison with a potassium ion channel.  All the gathered computational data reveals that the use of this or related sequences as K+ channels need to overcome significant energy barriers, even for the smaller Na+, if they are to be used as synthetic ion channels.

Although my technical knowledge of how to perform MDS is minimal, they contribute a very important part for the development of a molecular research project.  I think it will be great to have some fundamental MDS studies for some of our derivatives in relation to the ion movement not only in organic media, but also in aqueous environments.  As we have discovered in recent years, not all SGQs behave the same even if they have the same central guanine core in common.  Cations play a very important role in controlling these assemblies and I believe there is a need to put more effort in this regard, in particular with our system.  Any volunteers?

Categories: Lab-blog Tags: , , ,

Moving some of our lab blog posts to GQW

February 1, 2012 2 comments

From this semester onwards, the article synopses related to G-quadruplexes, which used to be posted in the blog in our lab website will be posted here. This is partly in preparation from transitioning away from the .Mac service (where the website is still hosted) since it will stop working in June of this year. In addition, using this blog is likely to increase the exposure of our posts as evidenced by the previous post. I’ll be announcing other changes in our web related activities soon.

In the meantime, continue to follow the guidelines in preparing your article synopses and postings:

An appropriate synopsis and comment should contain the following elements (1-3 for the blogger and 1-4 for the commenter):

  1. A brief synopsis of the article’s central idea (rationale, finding). In this part of your comment you must address explicitly the following issues: (a) What is the significance of the article? (b) How novel are the results? (c) Is the length of the manuscript appropriate to its contents? (c) What would you have done differently regarding this issue?
  2. A critical assessment of the experimental methods & techniques. In this part of your comment you must address explicitly the following issues: (a) Did the authors performed appropriate control experiments? (b) Are the conclusions supported by the results? (c) Are the references appropriate and correct? (d) Whenever applicable, is the characterization provided for new compounds appropriate with regard to identity and purity? (e) What would you have done differently regarding this issue?
  3. A critical assessment of the narrative. In this part of your comment you must addressexplicitly the following issues: (a) Is the narrative engaging? (b) Was the problem put in the proper perspective? (c) Did the authors do a good job explaining the significance of their findings? (d) What would you have done differently regarding this issue?
  4. A constructive criticism of the blogger’s synopsis. In this part of your comment you must address explicitly the following issues: (a) Was the synopsis well written (spelling and grammar)? (b) Could a person with a general knowledge of chemistry be able to grasp the fundamentals of the article being discussed? (c) Did the blogger addressed the issues i-iii of these guidelines? (d) What do you think of the blogger’s pictorial representation of the article? (e) Did the blogger used supplementary material to aid in the understanding of his/her synopsis (e.g. hyperlinks)  (d) What advice can you give to the blogger to improve his/her future synopses?
Categories: blogging, Lab-blog Tags: ,

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.