Biomaterial Database

G-quadruplexes as therapeutic targets. 2000

S Neidle, and M A Read

CRC Biomolecular Structure Unit, Chester Beatty Laboratories, The Institute of Cancer Research, Fulham Road, London SW3 6JB, United Kingdom. s.neidle@icr.ac.uk

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.

UI	MeSH Term	Description	Entries
D008024	Ligands	A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)	Ligand
D009690	Nucleic Acid Conformation	The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.	DNA Conformation,RNA Conformation,Conformation, DNA,Conformation, Nucleic Acid,Conformation, RNA,Conformations, DNA,Conformations, Nucleic Acid,Conformations, RNA,DNA Conformations,Nucleic Acid Conformations,RNA Conformations
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D006147	Guanine
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000880	Anthraquinones	Compounds based on ANTHRACENES which contain two KETONES in any position. Substitutions can be in any position except on the ketone groups.	Anthracenedione,Anthracenediones,Anthranoid,Anthraquinone,Anthraquinone Compound,Anthraquinone Derivative,Dianthraquinones,Dianthrones,Anthranoids,Anthraquinone Compounds,Anthraquinone Derivatives,Compound, Anthraquinone,Derivative, Anthraquinone
D000970	Antineoplastic Agents	Substances that inhibit or prevent the proliferation of NEOPLASMS.	Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D016615	Telomere	A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.	Telomeres
D054856	G-Quadruplexes	Higher-order DNA and RNA structures formed from guanine-rich sequences. They are formed around a core of at least 2 stacked tetrads of hydrogen-bonded GUANINE bases. They can be formed from one two or four separate strands of DNA (or RNA) and can display a wide variety of topologies, which are a consequence of various combinations of strand direction, length, and sequence. (From Nucleic Acids Res. 2006;34(19):5402-15)	DNA G-Quadruplexes,DNA, Quadruplex,G-Quadruplexes, DNA,G-Quadruplexes, RNA,Guanine-Quadruplexes,Guanine-Quartets,Guanine-Tetrads,Quadruplex DNA,RNA, G-Quadruplexes,Tetraplex DNA,DNA G Quadruplexes,DNA, Tetraplex,G Quadruplexes,G Quadruplexes, DNA,G Quadruplexes, RNA,G-Quadruplexes RNA,G-Quadruplexes RNAs,Guanine Quadruplexes,Guanine Quartets,Guanine Tetrads,Guanine-Quartet,Guanine-Tetrad,RNA G-Quadruplexes,RNA, G Quadruplexes,RNAs, G-Quadruplexes