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A three-repeat human telomeric sequence is shown to associate with a single-repeat human telomeric sequence, forming a structure called the (3+1) G-quadruplex assembly. In this assembly, three G-tracts are oriented in one direction and the fourth in the opposite direction.
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Zhang N., Phan A.T., and Patel D.J. (3 + 1) Assembly of three human telomeric repeats into an asymmetric dimeric G-quadruplex. J Am Chem Soc 127 (2005) 17277-17285. A three-repeat human telomeric sequence is shown to associate with a single-repeat human telomeric sequence, forming a structure called the (3+1) G-quadruplex assembly. In this assembly, three G-tracts are oriented in one direction and the fourth in the opposite direction.
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Two different G-rich sequences containing four G-tracts from the c-myc promoter form a propeller-type intramolecular G-quadruplex. Besides loops containing two or six residues, single-residue (A or T) double-chain-reversal loops were observed systematically to bridge three layers of G-tetrads. This study suggested that a single residue forms the most stable double-chain-reversal loop bridging three G-tetrad layers, and a six-residue loop is less stable than a two-residue loop.
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Hazel P., Huppert J., Balasubramanian S., and Neidle S. Loop-length-dependent folding of G-quadruplexes. J Am Chem Soc 126 (2004) 16405-16415. This study combined spectroscopic and simulation techniques to suggest that a single residue forms the most stable double-chain-reversal loop bridging three G-tetrad layers. Longer linkers form less stable double-chain-reversal loops and prefer to form different types of loop connections.
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A DNA fragment containing five G-tracts from the c-myc promoter forms a novel G-quadruplex fold, which comprises a core of three stacked G-tetrads formed by four parallel G-tracts with all anti guanines and a snapback 3′-end syn guanine. Study of the interaction of this G-quadruplex with four different ligands indicated that they all stack on the top of the G-tetrad core. In particular, TMPyP4 binds to this G-quadruplex in slow exchange; the structure of the G-quadruplex-TMPyP4 complex revealed how stacking and electrostatic interactions contribute to the stability of the complex. This structural information provides a platform for the design of anticancer drugs that target multi-G-tract sequences found in c-myc and other oncogenic promoters, as well as in telomeres.
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Phan A.T., Kuryavyi V., Gaw H.Y., and Patel D.J. Small-molecule interaction with a five-guanine-tract G-quadruplex structure from the human MYC promoter. Nat Chem Biol 1 (2005) 167-173. A DNA fragment containing five G-tracts from the c-myc promoter forms a novel G-quadruplex fold, which comprises a core of three stacked G-tetrads formed by four parallel G-tracts with all anti guanines and a snapback 3′-end syn guanine. Study of the interaction of this G-quadruplex with four different ligands indicated that they all stack on the top of the G-tetrad core. In particular, TMPyP4 binds to this G-quadruplex in slow exchange; the structure of the G-quadruplex-TMPyP4 complex revealed how stacking and electrostatic interactions contribute to the stability of the complex. This structural information provides a platform for the design of anticancer drugs that target multi-G-tract sequences found in c-myc and other oncogenic promoters, as well as in telomeres.
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An interlocked dimeric parallel-stranded DNA quadruplex: a potent inhibitor of HIV-1 integrase
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+ solution. Within each 16-nucleotide monomeric subunit, all G-stretches are parallel and all guanines are anti with the exception of G1, which is syn. Dimer formation is achieved through the mutual pairing of G1 of one monomer with G2, G6 and G13 of the other monomer, to complete G·G·G·G tetrad formation. Assays on loop-modified sequences suggested a new strategy for the potential design of improved HIV-1 integrase inhibitors.
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+ solution. Within each 16-nucleotide monomeric subunit, all G-stretches are parallel and all guanines are anti with the exception of G1, which is syn. Dimer formation is achieved through the mutual pairing of G1 of one monomer with G2, G6 and G13 of the other monomer, to complete G·G·G·G tetrad formation. Assays on loop-modified sequences suggested a new strategy for the potential design of improved HIV-1 integrase inhibitors.
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