@article{Do2011, abstract = {G-rich oligonucleotides T30695 (or T30923), with the sequence of (GGGT)(4), and T40214, with the sequence of (GGGC)(4), have been reported to exhibit anti-HIV and anticancer activity. Here we report on the structure of a dimeric G-quadruplex adopted by a derivative of these sequences in K(+) solution. It comprises two identical propeller-type parallel-stranded G-quadruplex subunits each containing three G-tetrad layers that are stacked via the 5'-5' interface. We demonstrated control over the stacking of the two monomeric subunits by sequence modifications. Our analysis of possible structures at the stacking interface provides a general principle for stacking of G-quadruplexes, which could have implications for the assembly and recognition of higher-order G-quadruplex structures.}, author = {Do, Ngoc Quang and Lim, Kah Wai and Teo, Ming Hoon and Heddi, Brahim and Phan, Anh Tuân}, doi = {10.1093/nar/gkr539}, journal = {Nucleic Acids Research}, month = {aug}, pages = {9448-9457}, title = {Stacking of G-quadruplexes: NMR structure of a G-rich oligonucleotide with potential anti-HIV and anticancer activity†}, url = {https://doi.org/10.1093/nar/gkr539}, volume = {39}, year = {2011} } @article{Heddi2011, abstract = {G-quadruplex structures formed by DNA at the human telomeres are attractive anticancer targets. Human telomeric sequences can adopt a diverse range of intramolecular G-quadruplex conformations: a parallel-stranded conformation was observed in the crystalline state, while at least four other forms were seen in K(+) solution, raising the question of which conformation is favored in crowded cellular environment. Here, we report the first NMR structure of a human telomeric G-quadruplex in crowded solution. We show that four different G-quadruplex conformations are converted to a propeller-type parallel-stranded G-quadruplex in K(+)-containing crowded solution due to water depletion. This study also reveals the formation of a new higher-order G-quadruplex structure under molecular crowding conditions. Our molecular dynamics simulations of solvent distribution provide insights at molecular level on the formation of parallel-stranded G-quadruplex in environment depleted of water. These results regarding human telomeric DNA can be extended to oncogenic promoters and other genomic G-rich sequences.}, author = {Heddi, Brahim and Phan, Anh Tuân}, doi = {10.1021/ja200786q}, journal = {Journal of the American Chemical Society}, month = {jun}, pages = {9824-9833}, title = {Structure of Human Telomeric DNA in Crowded Solution}, url = {https://oadoi.org/10.1021/ja200786q}, volume = {133}, year = {2011} } @article{Kuryavyi2010, abstract = {Previous studies have demonstrated that nuclease hypersensitivity regions of several proto-oncogenic DNA promoters, situated upstream of transcription start sites, contain guanine-rich tracts that form intramolecular G-quadruplexes stabilized by stacked G•G•G•G tetrads in monovalent cation solution. The human c-kit oncogenic promoter, an important target in the treatment of gastrointestinal tumors, contains two such stretches of guanine-rich tracts, designated c-kit1 and c-kit2. Our previous nuclear magnetic resonance (NMR)-based studies reported on the novel G-quadruplex scaffold of the c-kit1 promoter in K+-containing solution, where we showed for the first time that even an isolated guanine was involved in G-tetrad formation. These NMR-based studies are now extended to the c-kit2 promoter, which adopts two distinct all-parallel-stranded conformations in slow exchange, one of which forms a monomeric G-quadruplex (form-I) in 20 mM K+-containing solution and the other a novel dimeric G-quadruplex (form-II) in 100 mM K+-containing solution. The c-kit2 promoter dimeric form-II G-quadruplex adopts an unprecedented all-parallel-stranded topology where individual c-kit2 promoter strands span a pair of three-G-tetrad-layer-containing all-parallel-stranded G-quadruplexes aligned in a 3′ to 5′-end orientation, with stacking continuity between G-quadruplexes mediated by a sandwiched A•A non-canonical pair. We propose that strand exchange during recombination events within guanine-rich segments, could potentially be mediated by a synapsis intermediate involving an intergenic parallel-stranded dimeric G-quadruplex.}, author = {Kuryavyi, Vitaly and Phan, Anh Tuân and Patel, Dinshaw J.}, doi = {10.1093/nar/gkq558}, journal = {Nucleic Acids Research}, month = {jun}, pages = {6757-6773}, title = {Solution structures of all parallel-stranded monomeric and dimeric G-quadruplex scaffolds of the human c-kit2 promoter}, url = {http://dx.doi.org/10.1093/nar/gkq558}, volume = {38}, year = {2010} } @article{Lech2011, abstract = {Understanding the fundamentals of G-quadruplex formation is important both for targeting G-quadruplexes formed by natural sequences and for engineering new G-quadruplexes with desired properties. Using a combination of experimental and computational techniques, we have investigated the effects of site-specific substitution of a guanine with C8-modified guanine derivatives, including 8-bromo-guanine, 8-O-methyl-guanine, 8-amino-guanine, and 8-oxo-guanine, within a well-defined (3 + 1) human telomeric G-quadruplex platform. The effects of substitutions on the stability of the G-quadruplex were found to depend on the type and position of the modification among different guanines in the structure. An interesting modification-dependent NMR chemical-shift effect was observed across basepairing within a guanine tetrad. This effect was reproduced by ab initio quantum mechanical computations, which showed that the observed variation in imino proton chemical shift is largely influenced by changes in hydrogen-bond geometry within the guanine tetrad.}, author = {Lech, Christopher Jacques and Cheow Lim, Joefina Kim and Wen Lim, Jocelyn Mei and Lim, Joefina Kim Cheow and Lim, Jocelyn Mei Wen and Amrane, Samir and Heddi, Brahim and Phan, Anh Tuân}, doi = {10.1016/j.bpj.2011.08.049}, journal = {Biophysical Journal}, month = {oct}, pages = {1987-1998}, title = {Effects of Site-Specific Guanine C8-Modifications on an Intramolecular DNA G-Quadruplex}, url = {https://doi.org/10.1016/j.bpj.2011.08.049}, volume = {101}, year = {2011} } @article{Lim2009, abstract = {Short contiguous arrays of variant CTAGGG repeats in the human telomere are unstable in the male germline and somatic cells, suggesting formation of unusual structures by this repeat type. Here, we report on the structure of an intramolecular G-quadruplex formed by DNA sequences containing four human telomeric variant CTAGGG repeats in potassium solution. Our results reveal a new robust antiparallel G-quadruplex fold involving two G-tetrads sandwiched between a G·C base pair and a G·C·G·C tetrad, which could represent a new platform for drug design targeted to human telomeric DNA. ; This paper was published as Nucleic Acids Research, 2009, 37 (18), pp. 6239-6248. It is also available from http://nar.oxfordjournals.org/content/37/18/6239.abstract?sid=405b5e19-5c83-4d64-8a22-3e4df248de3a. Doi: 10.1093/nar/gkp630}, author = {Lim, Kah Wai and Alberti, Patrizia and Guédin, Aurore and Lacroix, Laurent and Riou, Jean-François and Royle, Nicola J. and Mergny, Jean-Louis and Phan, Anh Tuân}, doi = {10.1093/nar/gkp630}, month = {aug}, title = {Sequence variant (CTAGGG)n in the human telomere favors a G-quadruplex structure containing a G·C·G·C tetrad}, url = {http://dx.doi.org/10.1093/nar/gkp630}, year = {2009} } @article{Lim2010, author = {Lim, Kah Wai and Lacroix, Laurent and Yue, Doris Jia En and Lim, Joefina Kim Cheow and Lim, Jocelyn Mei Wen and Phan, Anh Tuân}, doi = {10.1021/ja101252n}, journal = {Journal of the American Chemical Society}, month = {aug}, pages = {12331-12342}, title = {Coexistence of Two Distinct G-Quadruplex Conformations in the hTERT Promoter}, url = {https://oadoi.org/10.1021/ja101252n}, volume = {132}, year = {2010} } @article{Martadinata2011, author = {Martadinata, Herry and Heddi, Brahim and Lim, Kah Wai and Phan, Anh Tuân}, doi = {10.1021/bi200569f}, journal = {Biochemistry}, month = {jul}, pages = {6455-6461}, title = {Structure of Long Human Telomeric RNA (TERRA): G-Quadruplexes Formed by Four and Eight UUAGGG Repeats Are Stable Building Blocks}, url = {https://oadoi.org/10.1021/bi200569f}, volume = {50}, year = {2011} } @article{Mendez-Bermudez2009, abstract = {A number of different processes that impact on telomere length dynamics have been identified but factors that affect the turnover of repeats located proximally within the telomeric DNA are poorly defined. We have identified a particular repeat type (CTAGGG) that is associated with an extraordinarily high mutation rate (20% per gamete) in the male germline. The mutation rate is affected by the length and sequence homogeneity of the (CTAGGG)n array. This level of instability was not seen with other sequence-variant repeats, including the TCAGGG repeat type that has the same composition. Telomeres carrying a (CTAGGG)n array are also highly unstable in somatic cells with the mutation process resulting in small gains or losses of repeats that also occasionally result in the deletion of the whole (CTAGGG)n array. These sequences are prone to quadruplex formation in vitro but adopt a different topology from (TTAGGG)n (see accompanying article). Interestingly, short (CTAGGG)2 oligonucleotides induce a DNA damage response (γH2AX foci) as efficiently as (TTAGGG)2 oligos in normal fibroblast cells, suggesting they recruit POT1 from the telomere. Moreover, in vitro assays show that (CTAGGG)n repeats bind POT1 more efficiently than (TTAGGG)n or (TCAGGG)n. We estimate that 7% of human telomeres contain (CTAGGG)n repeats and when present, they create additional problems that probably arise during telomere replication. ; This paper was published as Nucleic Acids Research, 2009, 37 (18), pp. 6225-6238. It is also available from http://www.nar.oxfordjournals.org/content/37/18/6225. Doi: 10.1093/nar/gkp629}, author = {Mendez-Bermudez, Aaron and Hills, Mark and Pickett, Hilda A. and Phan, Anh Tuân and Mergny, Jean-Louis and Riou, Jean-François and Royle, Nicola J.}, doi = {10.1093/nar/gkp629}, month = {aug}, title = {Human telomeres that contain (CTAGGG)n repeats show replication dependent instability in somatic cells and the male germline}, url = {http://dx.doi.org/10.1093/nar/gkp629}, year = {2009} } @article{Mukundan2011, abstract = {T30177 is a G-rich oligonucleotide with the sequence (GTGGTGGGTGGGTGGGT) which inhibits the HIV-1 integrase activity at nanomolar concentrations. Here we show that this DNA sequence forms in K+ solution a dimeric G-quadruplex structure comprising a total of six G-tetrad layers through the stacking of two propeller-type parallel-stranded G-quadruplex subunits at their 5′-end. All twelve guanines in the sequence participate in the G-tetrad formation, despite the interruption in the first G-tract by a thymine, which forms a bulge between two adjacent G-tetrads. In this work, we also propose a simple analytical approach to stoichiometry determination using concentration-dependent melting curves.}, author = {Mukundan, Vineeth Thachappilly and Do, Ngoc Quang and Phan, Anh Tuân}, doi = {10.1093/nar/gkr540}, journal = {Nucleic Acids Research}, month = {jul}, pages = {8984-8991}, title = {HIV-1 integrase inhibitor T30177 forms a stacked dimeric G-quadruplex structure containing bulges}, url = {https://doi.org/10.1093/nar/gkr540}, volume = {39}, year = {2011} } @article{Phan2011, abstract = {We have determined the solution structure of the complex between an arginine-glycine-rich RGG peptide from the human fragile X mental retardation protein (FMRP) and an in vitro-selected guanine-rich (G-rich) sc1 RNA. The bound RNA forms a newly discovered G-quadruplex separated from the flanking duplex stem by a mixed junctional tetrad. The RGG peptide is positioned along the major groove of the RNA duplex, with the G-quadruplex forcing a sharp turn of R(10)GGGGR(15) at the duplex-quadruplex junction. Arg10 and Arg15 form cross-strand specificity-determining intermolecular hydrogen bonds with the major-groove edges of guanines of adjacent Watson-Crick G•C pairs. Filter-binding assays on RNA and peptide mutations identify and validate contributions of peptide-RNA intermolecular contacts and shape complementarity to molecular recognition. These findings on FMRP RGG domain recognition by a combination of G-quadruplex and surrounding RNA sequences have implications for the recognition of other genomic G-rich RNAs.}, author = {Phan, Anh Tuân and Kuryavyi, Vitaly and Darnell, Jennifer C. and Serganov, Alexander and Majumdar, Ananya and Ilin, Serge and Raslin, Tanya and Polonskaia, Anna and Chen, Cynthia and Clain, David and Darnell, Robert B. and Patel, Dinshaw J.}, doi = {10.1038/nsmb.2064}, journal = {Nature Structural and Molecular Biology}, month = {jun}, pages = {796-804}, title = {Structure-function studies of FMRP RGG peptide recognition of an RNA duplex-quadruplex junction}, url = {http://www.nature.com/articles/nsmb.2064.pdf}, volume = {18}, year = {2011} } @article{Swaminathan2011, abstract = {AbstractThe use of nanowires (NWs) for labeling, sensing, and sorting is the basis of detecting biomolecules attached on NWs by optical and magnetic properties. In spite of many advantages, the use of biomolecules-attached NWs sensing by photoelectrochemical (PEC) study is almost non-existent. In this article, the PEC study of dye-attached single-stranded DNA on Au NWs and Au-Ni-Au multilayer NWs prepared by pulse electrodeposition are investigated. Owing to quantum-quenching effect, the multilayer Au NWs exhibit low optical absorbance when compared with Au NWs. The tagged Au NWs show good fluorescence (emission) at 570 nm, indicating significant improvement in the reflectivity. Optimum results obtained for tagged Au NWs attached on functionalized carbon electrodes and its PEC behavior is also presented. A twofold enhancement in photocurrent is observed with an average dark current of 10 μA for Au NWs coated on functionalized sensing electrode. The importance of these PEC and optical studies provides an inexpensive and facile processing platform for Au NWs that may be suitable for biolabeling applications.}, author = {Swaminathan, Viswanathan and Liew, Hwi Fen and Lew, Wen Siang and Hu, Lanying and Phan, Anh Tuan}, doi = {10.1186/1556-276x-6-535}, journal = {Nanoscale Research Letters}, month = {jan}, title = {Photoelectrochemical studies of DNA-tagged biomolecules on Au and Au/Ni/Au multilayer nanowires}, url = {http://dx.doi.org/10.1186/1556-276x-6-535}, volume = {6}, year = {2011} } @article{Yue2011, author = {Yue, Doris Jia En and Lim, Kah Wai and Phan, Anh Tuân}, doi = {10.1021/ja204197d}, journal = {Journal of the American Chemical Society}, month = {aug}, pages = {11462-11465}, title = {Formation of (3+1) G-Quadruplexes with a Long Loop by Human Telomeric DNA Spanning Five or More Repeats}, url = {https://oadoi.org/10.1021/ja204197d}, volume = {133}, year = {2011} }