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PDBsum entry 2a5r
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PDB id:
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DNA
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Title:
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Complex of tetra-(4-n-methylpyridyl) porphin with monomeric parallel- stranded DNA tetraplex, snap-back 3+1 3' g-tetrad, single-residue chain reversal loops, gag triad in the context of gaag diagonal loop, c-myc promoter, nmr, 6 struct.
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Structure:
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5'-d( Tp Gp Ap Gp Gp Gp Tp Gp Gp Ip Gp Ap Gp Gp Gp Tp Gp Gp Gp Gp Ap Ap Gp G)-3'. Chain: a
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Other_details: c-myc gene
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NMR struc:
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6 models
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Authors:
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A.T.Phan,V.V.Kuryavyi,H.Y.Gaw,D.J.Patel
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Key ref:
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A.T.Phan
et al.
(2005).
Small-molecule interaction with a five-guanine-tract G-quadruplex structure from the human MYC promoter.
Nat Chem Biol,
1,
167-173.
PubMed id:
DOI:
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Date:
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30-Jun-05
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Release date:
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26-Jul-05
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Headers
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References
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T-G-A-G-G-G-T-G-G-I-G-A-G-G-G-T-G-G-G-G-A-A-G-G
24 bases
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DOI no:
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Nat Chem Biol
1:167-173
(2005)
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PubMed id:
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Small-molecule interaction with a five-guanine-tract G-quadruplex structure from the human MYC promoter.
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A.T.Phan,
V.Kuryavyi,
H.Y.Gaw,
D.J.Patel.
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ABSTRACT
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It has been widely accepted that DNA can adopt other biologically relevant
structures beside the Watson-Crick double helix. One recent important example is
the guanine-quadruplex (G-quadruplex) structure formed by guanine tracts found
in the MYC (or c-myc) promoter region, which regulates the transcription of the
MYC oncogene. Stabilization of this G-quadruplex by ligands, such as the
cationic porphyrin TMPyP4, decreases the transcriptional level of MYC. Here, we
report the first structure of a DNA fragment containing five guanine tracts from
this region. An unusual G-quadruplex fold, which was derived from NMR restraints
using unambiguous model-independent resonance assignment approaches, involves a
core of three stacked guanine tetrads formed by four parallel guanine tracts
with all anti guanines and a snapback 3'-end syn guanine. We have determined the
structure of the complex formed between this G-quadruplex and TMPyP4. This
structural information, combined with details of small-molecule interaction,
provides a platform for the design of anticancer drugs targeting
multi-guanine-tract sequences that are found in the MYC and other oncogenic
promoters, as well as in telomeres.
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Selected figure(s)
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Figure 2.
(a) Stereo view of eight superposed refined structures of the
Pu24I quadruplex.
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Figure 5.
(a) Side view. (b) Top view. Pu24I quadruplex is colored
green; TMPyP4 is colored red.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Chem Biol
(2005,
1,
167-173)
copyright 2005.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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H.Bertrand,
A.Granzhan,
D.Monchaud,
N.Saettel,
R.Guillot,
S.Clifford,
A.Guédin,
J.L.Mergny,
and
M.P.Teulade-Fichou
(2011).
Recognition of G-quadruplex DNA by triangular star-shaped compounds: with or without side chains?
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Chemistry,
17,
4529-4539.
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J.Dash,
Z.A.Waller,
G.D.Pantoş,
and
S.Balasubramanian
(2011).
Synthesis and binding studies of novel diethynyl-pyridine amides with genomic promoter DNA G-quadruplexes.
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Chemistry,
17,
4571-4581.
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M.H.Li,
Q.Luo,
X.G.Xue,
and
Z.S.Li
(2011).
Molecular dynamics studies of the 3D structure and planar ligand binding of a quadruplex dimer.
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J Mol Model,
17,
515-526.
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S.Balasubramanian,
L.H.Hurley,
and
S.Neidle
(2011).
Targeting G-quadruplexes in gene promoters: a novel anticancer strategy?
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Nat Rev Drug Discov,
10,
261-275.
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Y.J.Lu,
S.C.Yan,
F.Y.Chan,
L.Zou,
W.H.Chung,
W.L.Wong,
B.Qiu,
N.Sun,
P.H.Chan,
Z.S.Huang,
L.Q.Gu,
and
K.Y.Wong
(2011).
Benzothiazole-substituted benzofuroquinolinium dye: a selective switch-on fluorescent probe for G-quadruplex.
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Chem Commun (Camb),
47,
4971-4973.
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A.Bugaut,
R.Rodriguez,
S.Kumari,
S.T.Hsu,
and
S.Balasubramanian
(2010).
Small molecule-mediated inhibition of translation by targeting a native RNA G-quadruplex.
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Org Biomol Chem,
8,
2771-2776.
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J.E.Johnson,
K.Cao,
P.Ryvkin,
L.S.Wang,
and
F.B.Johnson
(2010).
Altered gene expression in the Werner and Bloom syndromes is associated with sequences having G-quadruplex forming potential.
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Nucleic Acids Res,
38,
1114-1122.
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P.Wang,
C.H.Leung,
D.L.Ma,
S.C.Yan,
and
C.M.Che
(2010).
Structure-based design of platinum(II) complexes as c-myc oncogene down-regulators and luminescent probes for G-quadruplex DNA.
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Chemistry,
16,
6900-6911.
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Q.Yang,
J.Xiang,
S.Yang,
Q.Li,
Q.Zhou,
A.Guan,
X.Zhang,
H.Zhang,
Y.Tang,
and
G.Xu
(2010).
Verification of specific G-quadruplex structure by using a novel cyanine dye supramolecular assembly: II. The binding characterization with specific intramolecular G-quadruplex and the recognizing mechanism.
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Nucleic Acids Res,
38,
1022-1033.
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R.Basundra,
A.Kumar,
S.Amrane,
A.Verma,
A.T.Phan,
and
S.Chowdhury
(2010).
A novel G-quadruplex motif modulates promoter activity of human thymidine kinase 1.
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FEBS J,
277,
4254-4264.
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S.Sparapani,
S.Bellini,
M.Gunaratnam,
S.M.Haider,
A.Andreani,
M.Rambaldi,
A.Locatelli,
R.Morigi,
M.Granaiola,
L.Varoli,
S.Burnelli,
A.Leoni,
and
S.Neidle
(2010).
Bis-guanylhydrazone diimidazo[1,2-a:1,2-c]pyrimidine as a novel and specific G-quadruplex binding motif.
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Chem Commun (Camb),
46,
5680-5682.
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T.Wilson,
M.P.Williamson,
and
J.A.Thomas
(2010).
Differentiating quadruplexes: binding preferences of a luminescent dinuclear ruthenium(II) complex with four-stranded DNA structures.
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Org Biomol Chem,
8,
2617-2621.
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D.R.Boer,
A.Canals,
and
M.Coll
(2009).
DNA-binding drugs caught in action: the latest 3D pictures of drug-DNA complexes.
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Dalton Trans,
(),
399-414.
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F.Fogolari,
H.Haridas,
A.Corazza,
P.Viglino,
D.Corà,
M.Caselle,
G.Esposito,
and
L.E.Xodo
(2009).
Molecular models for intrastrand DNA G-quadruplexes.
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BMC Struct Biol,
9,
64.
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G.D.Balkwill,
T.P.Garner,
and
M.S.Searle
(2009).
Folding of single-stranded DNA quadruplexes containing an autonomously stable mini-hairpin loop.
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Mol Biosyst,
5,
542-547.
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H.Bertrand,
S.Bombard,
D.Monchaud,
E.Talbot,
A.Guédin,
J.L.Mergny,
R.Grünert,
P.J.Bednarski,
and
M.P.Teulade-Fichou
(2009).
Exclusive platination of loop adenines in the human telomeric G-quadruplex.
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Org Biomol Chem,
7,
2864-2871.
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J.Amato,
G.Oliviero,
E.De Pauw,
and
V.Gabelica
(2009).
Hybridization of short complementary PNAs to G-quadruplex forming oligonucleotides: An electrospray mass spectrometry study.
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Biopolymers,
91,
244-255.
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M.Tera,
K.Iida,
H.Ishizuka,
M.Takagi,
M.Suganuma,
T.Doi,
K.Shin-ya,
and
K.Nagasawa
(2009).
Synthesis of a potent G-quadruplex-binding macrocyclic heptaoxazole.
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Chembiochem,
10,
431-435.
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R.K.Thakur,
P.Kumar,
K.Halder,
A.Verma,
A.Kar,
J.L.Parent,
R.Basundra,
A.Kumar,
and
S.Chowdhury
(2009).
Metastases suppressor NM23-H2 interaction with G-quadruplex DNA within c-MYC promoter nuclease hypersensitive element induces c-MYC expression.
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Nucleic Acids Res,
37,
172-183.
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S.Balasubramanian,
and
S.Neidle
(2009).
G-quadruplex nucleic acids as therapeutic targets.
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Curr Opin Chem Biol,
13,
345-353.
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S.Neidle
(2009).
The structures of quadruplex nucleic acids and their drug complexes.
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Curr Opin Struct Biol,
19,
239-250.
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A.Bugaut,
and
S.Balasubramanian
(2008).
A sequence-independent study of the influence of short loop lengths on the stability and topology of intramolecular DNA G-quadruplexes.
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Biochemistry,
47,
689-697.
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A.K.Todd,
and
S.Neidle
(2008).
The relationship of potential G-quadruplex sequences in cis-upstream regions of the human genome to SP1-binding elements.
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Nucleic Acids Res,
36,
2700-2704.
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A.N.Lane,
J.B.Chaires,
R.D.Gray,
and
J.O.Trent
(2008).
Stability and kinetics of G-quadruplex structures.
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Nucleic Acids Res,
36,
5482-5515.
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D.Monchaud,
and
M.P.Teulade-Fichou
(2008).
A hitchhiker's guide to G-quadruplex ligands.
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Org Biomol Chem,
6,
627-636.
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J.D.Beaudoin,
and
J.P.Perreault
(2008).
Potassium ions modulate a G-quadruplex-ribozyme's activity.
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RNA,
14,
1018-1025.
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J.E.Johnson,
J.S.Smith,
M.L.Kozak,
and
F.B.Johnson
(2008).
In vivo veritas: using yeast to probe the biological functions of G-quadruplexes.
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Biochimie,
90,
1250-1263.
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J.Talib,
C.Green,
K.J.Davis,
T.Urathamakul,
J.L.Beck,
J.R.Aldrich-Wright,
and
S.F.Ralph
(2008).
A comparison of the binding of metal complexes to duplex and quadruplex DNA.
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Dalton Trans,
(),
1018-1026.
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S.Cogoi,
M.Paramasivam,
B.Spolaore,
and
L.E.Xodo
(2008).
Structural polymorphism within a regulatory element of the human KRAS promoter: formation of G4-DNA recognized by nuclear proteins.
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Nucleic Acids Res,
36,
3765-3780.
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T.M.Ou,
Y.J.Lu,
J.H.Tan,
Z.S.Huang,
K.Y.Wong,
and
L.Q.Gu
(2008).
G-quadruplexes: targets in anticancer drug design.
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ChemMedChem,
3,
690-713.
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W.C.Drewe,
and
S.Neidle
(2008).
Click chemistry assembly of G-quadruplex ligands incorporating a diarylurea scaffold and triazole linkers.
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Chem Commun (Camb),
(),
5295-5297.
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A.K.Todd,
S.M.Haider,
G.N.Parkinson,
and
S.Neidle
(2007).
Sequence occurrence and structural uniqueness of a G-quadruplex in the human c-kit promoter.
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Nucleic Acids Res,
35,
5799-5808.
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A.Matsugami,
Y.Xu,
Y.Noguchi,
H.Sugiyama,
and
M.Katahira
(2007).
Structure of a human telomeric DNA sequence stabilized by 8-bromoguanosine substitutions, as determined by NMR in a K+ solution.
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FEBS J,
274,
3545-3556.
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PDB code:
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C.Hounsou,
L.Guittat,
D.Monchaud,
M.Jourdan,
N.Saettel,
J.L.Mergny,
and
M.P.Teulade-Fichou
(2007).
G-Quadruplex Recognition by Quinacridines: a SAR, NMR, and Biological Study.
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ChemMedChem,
2,
655-666.
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PDB code:
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D.J.Patel,
A.T.Phan,
and
V.Kuryavyi
(2007).
Human telomere, oncogenic promoter and 5'-UTR G-quadruplexes: diverse higher order DNA and RNA targets for cancer therapeutics.
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Nucleic Acids Res,
35,
7429-7455.
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H.Bertrand,
S.Bombard,
D.Monchaud,
and
M.P.Teulade-Fichou
(2007).
A platinum-quinacridine hybrid as a G-quadruplex ligand.
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J Biol Inorg Chem,
12,
1003-1014.
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M.Webba da Silva
(2007).
Geometric formalism for DNA quadruplex folding.
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Chemistry,
13,
9738-9745.
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P.Podbevsek,
N.V.Hud,
and
J.Plavec
(2007).
NMR evaluation of ammonium ion movement within a unimolecular G-quadruplex in solution.
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Nucleic Acids Res,
35,
2554-2563.
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S.E.Evans,
M.A.Mendez,
K.B.Turner,
L.R.Keating,
R.T.Grimes,
S.Melchoir,
and
V.A.Szalai
(2007).
End-stacking of copper cationic porphyrins on parallel-stranded guanine quadruplexes.
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J Biol Inorg Chem,
12,
1235-1249.
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A.T.Phan,
V.Kuryavyi,
and
D.J.Patel
(2006).
DNA architecture: from G to Z.
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Curr Opin Struct Biol,
16,
288-298.
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J.J.Green,
S.Ladame,
L.Ying,
D.Klenerman,
and
S.Balasubramanian
(2006).
Investigating a quadruplex-ligand interaction by unfolding kinetics.
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J Am Chem Soc,
128,
9809-9812.
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M.Kaiser,
A.De Cian,
M.Sainlos,
C.Renner,
J.L.Mergny,
and
M.P.Teulade-Fichou
(2006).
Neomycin-capped aromatic platforms: quadruplex DNA recognition and telomerase inhibition.
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Org Biomol Chem,
4,
1049-1057.
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O.Kikin,
L.D'Antonio,
and
P.S.Bagga
(2006).
QGRS Mapper: a web-based server for predicting G-quadruplexes in nucleotide sequences.
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Nucleic Acids Res,
34,
W676-W682.
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S.Burge,
G.N.Parkinson,
P.Hazel,
A.K.Todd,
and
S.Neidle
(2006).
Quadruplex DNA: sequence, topology and structure.
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Nucleic Acids Res,
34,
5402-5415.
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Y.Xu,
and
H.Sugiyama
(2006).
Formation of the G-quadruplex and i-motif structures in retinoblastoma susceptibility genes (Rb).
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Nucleic Acids Res,
34,
949-954.
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M.Roitzsch,
and
B.Lippert
(2005).
Inverting the charges of natural nucleobase quartets: a planar platinum-purine quartet with pronounced sulfate affinity.
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Angew Chem Int Ed Engl,
45,
147-150.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
