Journal ArticleDOI
G-quadruplexes as therapeutic targets.
Stephen Neidle,Martin A. Read +1 more
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TLDR
Structural and mechanistic aspects of these quadruplex complexes are reviewed here, together with a discussion of the issues of selectivity/potency for quadruplex DNAs vs duplex DNA.Abstract:
G-quadruplexes as therapeutic targets. The ends of chromosomes (telomeres) consist of tandem repeats of guanine-rich sequences. In eukaryotics, telomeric DNA is single stranded for the final few hundred bases. These single- stranded sequences can fold into a variety of four-stranded structures (quadruplexes) held together by quartets of hydrogen-bonded guanine bases. The reverse transcriptase enzyme telomerase is responsible for maintaining telomeric DNA length in over 85% of cancer cells by catalyzing the synthesis of further telomeric repeats. Its substrate is the single-stranded 3'-telomeric end. Inhibition of telomere maintenance can be achieved by stabilization of a quadruplex structure for the telomere end. A variety of small molecules have been devised to achieve this, ranging from anthraquinones to porphyrins, acridines, and complex polycyclic systems. Structural and mechanistic aspects of these quadruplex complexes are reviewed here, together with a discussion of the issues of selectivity/potency for quadruplex DNAs vs duplex DNA.read more
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Supramolecular coordination: self-assembly of finite two- and three-dimensional ensembles.
TL;DR: In the early 1960s, the discovery of crown ethers and spherands by Pedersen, Lehn, and Cram3 led to the realization that small, complementary molecules can be made to recognize each other through non-covalent interactions such as hydrogen-bonding, charge-charge, donor-acceptor, π-π, van der Waals, hydrophilic and hydrophobic interactions to achieve these highly complex and often symmetrical architectures as mentioned in this paper.
Journal ArticleDOI
Human telomeric sequence forms a hybrid-type intramolecular G-quadruplex structure with mixed parallel/antiparallel strands in potassium solution
TL;DR: The folding structure of the human telomeric sequence in K+ solution determined by NMR demonstrates a novel, unprecedented intramolecular G-quadruplex folding topology with hybrid-type mixed parallel/antiparallel G-strands, and suggests a straightforward pathway for the secondary structure formation with effective packing within the extended human telomersic DNA.
Journal ArticleDOI
Human telomere, oncogenic promoter and 5′-UTR G-quadruplexes: diverse higher order DNA and RNA targets for cancer therapeutics
TL;DR: The review highlights recent solution NMR-based G-quadruplex structures formed by the four-repeat human telomere in K+ solution and the guanine-rich strands of c-myc, c-kit and variant bcl-2 oncogenic promoters, as well as a bimolecular G- quadruplex that targets HIV-1 integrase.
Journal ArticleDOI
From Cascaded Catalytic Nucleic Acids to Enzyme–DNA Nanostructures: Controlling Reactivity, Sensing, Logic Operations, and Assembly of Complex Structures
Journal ArticleDOI
Structure of the Hybrid-2 type intramolecular human telomeric G-quadruplex in K+ solution: insights into structure polymorphism of the human telomeric sequence
TL;DR: The first structure of the major intramolecular G-quadruplex formed in a native, non-modified human telomeric sequence in K+ solution is reported, a hybrid-type mixed parallel/antiparallel-G-stranded G- quadruplex, one end of which is covered by a novel T:A:T triple capping structure.
References
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Journal ArticleDOI
A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules
Wendy D. Cornell,Piotr Cieplak,Piotr Cieplak,Christopher I. Bayly,Christopher I. Bayly,Ian R. Gould,Ian R. Gould,Kenneth M. Merz,Kenneth M. Merz,David M. Ferguson,David M. Ferguson,David C. Spellmeyer,David C. Spellmeyer,Thomas R. Fox,James W. Caldwell,Peter A. Kollman +15 more
TL;DR: Weiner et al. as mentioned in this paper derived a new molecular mechanical force field for simulating the structures, conformational energies, and interaction energies of proteins, nucleic acids, and many related organic molecules in condensed phases.
Journal ArticleDOI
Specific association of human telomerase activity with immortal cells and cancer
Nam Woo Kim,Mieczyslaw A. Piatyszek,Karen R. Prowse,Calvin B. Harley,Michael D. West,Peter L. C. Ho,Gina M. Coviello,Woodring E. Wright,Scott L. Weinrich,Jerry W. Shay +9 more
TL;DR: A highly sensitive assay for measuring telomerase activity was developed in this paper, which showed that telomerases appear to be stringently repressed in normal human somatic tissues but reactivated in cancer, where immortal cells are likely required to maintain tumor growth.
Journal ArticleDOI
Telomeres shorten during ageing of human fibroblasts.
TL;DR: The amount and length of telomeric DNA in human fibroblasts does in fact decrease as a function of serial passage during ageing in vitro and possibly in vivo.
Journal ArticleDOI
A survey of telomerase activity in human cancer
Jerry W. Shay,Silvia Bacchetti +1 more
TL;DR: All major types of cancer have been screened and the presence of telomerase activity has been detected in the vast majority of cases, and a summary, in table form, of the current data is provided.
Journal ArticleDOI
Mammalian Telomeres End in a Large Duplex Loop
Jack D. Griffith,Laurey Comeau,Soraya Rosenfield,Rachel M. Stansel,Alessandro Bianchi,Heidi Moss,Titia de Lange +6 more
TL;DR: Electron microscopy reported here demonstrated that TRF2 can remodel linear telomeric DNA into large duplex loops (t loops) in vitro, which may provide a general mechanism for the protection and replication of telomeres.