Stabilization of guanine quadruplex DNA by the binding of porphyrins with cationic side arms

Yamashita, Takeshi; Uno, Tadayuki; Ishikawa, Yoshinobu

doi:10.1016/j.bmc.2005.01.041

Cited by 97 publications

(66 citation statements)

References 62 publications

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“…We used NMR to monitor the interaction of the Pu24I quadruplex with several small molecules that have been reported to bind G-quadruplexes: 34,[36][37][38] . Upon addition of ethidium, Hoechst 33258 and daunomycin to the solution of Pu24I, imino protons of the top G-tetrad's residues (G4, G13, G8 and G17) were most perturbed (shifted upfield and broadened), consistent with the stacking of these ligands on the top G-tetrad.…”

Section: Interaction Of Pu24i Quadruplex With Ligandsmentioning

confidence: 99%

Small-molecule interaction with a five-guanine-tract G-quadruplex structure from the human MYC promoter

et al. 2005

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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 (Gquadruplex) 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 modelindependent 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 TMPγP4. 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.Human c-MYC is a transcription factor that is central to regulation of cell growth, proliferation, differentiation and apoptosis [1][2][3][4] . The MYC (also known as c-myc) gene that encodes this protein is tightly regulated in normal cells and its aberrant overexpression is associated with the progression of many cancers 5 . An important element in the MYC promoter region, termed nuclease-hypersensitivity element III 1 (NHE III 1 ), controls up to 90% of total MYC transcription [6][7][8][9] . Previous studies have suggested that this element, composed of a pyrimidine-rich and a purine-rich strand, may form other structures beyond the canonical B-DNA Watson-Crick duplex 6,8,[10][11][12] . In particular, the 27-nucleotide (nt) purine-rich strand (Pu27) of this element, which contains six guanine tracts (Table 1), forms multiple G-quadruplex structures [12][13][14][15] built from the stacking of G·G·G·G tetrads 16 . Furthermore, the G-quadruplex structure(s) involving four central guanine tracts of Pu27 is biologically relevant, as its destabilization (by guanine-to-adenine mutations) and its Correspondence should be addressed to A.T.P. (phantuan@mskcc.org) or D.J.P. (pateld@mskcc.org). Accession codes. Protein Data Bank codes: The coordinates for the structures of Pu24I and the Pu24I-TMPyP4 complex have been deposited under accession codes 2A5P and 2A5R, respectively. Note: Supplementary information is available on the Nature Chemical Biology website. COMPETING INTERESTS STATEMENTThe authors declare that they have no competing financial interests. Here we present the structure of a 24-nt five-guanine-tract sequence from the guanine-rich strand of the MYC NHE III 1 in K + solution. The structure represents a unique intramolecular parallel-stranded foldback G-quadruplex, in which a guanine from the 3′ tail is plugged back into the core...

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Section: Interaction Of Pu24i Quadruplex With Ligandsmentioning

confidence: 99%

Small-molecule interaction with a five-guanine-tract G-quadruplex structure from the human MYC promoter

et al. 2005

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“…As is well known, intercalation of porphyrins between the base pairs of double helix DNA leads to about a 15-nm red shift and almost 35% hypochromicity of the porphyrins soret band. A small red shift (about 6-8 nm) and hypochromicity (10%) or even hyperchromicity of the soret band are observed due to outside binding without stacking of porphyrin to double helix DNA [20,21]. These spectral characteristics have been determined for long pieces of duplex DNA but not for the quadruplex DNA.…”

Section: Absorption Spectroscopymentioning

confidence: 98%

Interaction of hemin with quadruplex DNA

et al. 2016

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A DNA enzyme with peroxidase activity is a G-quadruplex-based DNAzyme formed by hemin and G-quadruplex DNA. Activity of peroxide DNAzymes can be influenced by the structure of quadruplex DNA. In this investigation, the interaction of hemin with T30695 G-quadruplex DNA is evaluated. Molecular dynamic simulation indicates that the binding mode of hemin to G-quadruplex DNA is end-stacking, which is consistent with absorption spectroscopy. Based on fluorescence spectroscopy, hemin ejects thiazole orange from bases of four-strand DNA. Circular dichroism spectra showed that no alteration occurs in this type of DNA structure.

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“…Several different models of TMPyP4 binding to quadruplexes have been proposed on the basis of structural, spectroscopic, calorimetric, or computational studies. Features of various models include the intercalative binding of the drug between two adjacent G-quartets [8][9][10][11][12], and/or stacking on the external Gtetrads or with the loops of the quadruplexes [8,[13][14][15][16][17] and a weaker external binding [12,[18][19][20][21][22][23]. This is further complicated by the intrinsic structural polymorphism of quadruplexes.…”

Section: Introductionmentioning

confidence: 97%

Spectroscopic study on the binding of porphyrins to (G4T4G4)4 parallel G-quadruplex

Wei

Wang

Zhang

2010

Biophysical Chemistry

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Stabilization of guanine quadruplex DNA by the binding of porphyrins with cationic side arms

Cited by 97 publications

References 62 publications

Small-molecule interaction with a five-guanine-tract G-quadruplex structure from the human MYC promoter

Small-molecule interaction with a five-guanine-tract G-quadruplex structure from the human MYC promoter

Interaction of hemin with quadruplex DNA

Spectroscopic study on the binding of porphyrins to (G4T4G4)4 parallel G-quadruplex

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