TITLE

General Cell-Binding Activity of Intramolecular G-Quadruplexes with Parallel Structure

AUTHOR(S)
Chang, Tianjun; Qi, Cui; Meng, Jie; Zhang, Nan; Bing, Tao; Yang, Xianda; Cao, Zehui; Shangguan, Dihua
PUB. DATE
April 2013
SOURCE
PLoS ONE;Apr2013, Vol. 8 Issue 4, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
: G-quadruplexes (G4s) are four-stranded nucleic acid structures adopted by some repetitive guanine-rich sequences. Putative G-quadruplex-forming sequences (PQSs) are highly prevalent in human genome. Recently some G4s have been reported to have cancer-selective antiproliferative activity. A G4 DNA, AS1411, is currently in phase II clinical trials as an anticancer agent, which is reported to bind tumor cells by targeting surface nucleolin. AS1411 also has been extensively investigated as a target-recognition element for cancer cell specific drug delivery or cancer cell imaging. Here we show that, in addition to AS1411, intramolecular G4s with parallel structure (including PQSs in genes) have general binding activity to many cell lines with different affinity. The binding of these G4s compete with each other, and their targets are certain cellular surface proteins. The tested G4s exhibit enhanced cellular uptake than non-G4 sequences. This uptake may be through the endosome/lysosome pathway, but it is independent of cellular binding of the G4s. The tested G4s also show selective antiproliferative activity that is independent of their cellular binding. Our findings provide new insight into the molecular recognition of G4s by cells; offer new clues for understanding the functions of G4s in vivo, and may extend the potential applications of G4s.
ACCESSION #
87679092

 

Related Articles

  • G-Quadruplex Structures in the Human Genome as Novel Therapeutic Targets. Bidzinska, Joanna; Cimino-Reale, Graziella; Zaffaroni, Nadia; Folini, Marco // Molecules;Oct2013, Vol. 18 Issue 10, p12368 

    G-quadruplexes are secondary structures that may form within guanine-rich nucleic acid sequences. Telomeres have received much attention in this regard since they can fold into several distinct intramolecular G-quadruplexes, leading to the rational design and development of...

  • Conformation and Stability of Intramolecular Telomeric G-Quadruplexes: Sequence Effects in the Loops. Sattin, Giovanna; Artese, Anna; Nadai, Matteo; Costa, Giosuè; Parrotta, Lucia; Alcaro, Stefano; Palumbo, Manlio; Richter, Sara N. // PLoS ONE;Dec2013, Vol. 8 Issue 12, p1 

    Telomeres are guanine-rich sequences that protect the ends of chromosomes. These regions can fold into G-quadruplex structures and their stabilization by G-quadruplex ligands has been employed as an anticancer strategy. Genetic analysis in human telomeres revealed extensive allelic variation...

  • Pentose Phosphate Pathway Function Affects Tolerance to the G-Quadruplex Binder TMPyP4. Andrew, Elizabeth J.; Merchan, Stephanie; Lawless, Conor; Banks, A. Peter; Wilkinson, Darren J.; Lydall, David // PLoS ONE;Jun2013, Vol. 8 Issue 6, p1 

    G-quadruplexes form in guanine-rich regions of DNA and the presence of these structures at telomeres prevents the activity of telomerase in vitro. Ligands such as the cationic porphyrin TMPyP4 stabilise G-quadruplexes and are therefore under investigation for their potential use as anti-cancer...

  • Kinetic Partitioning Modulates Human Telomere DNA G-Quadruplex Structural Polymorphism. Long, Xi; Stone, Michael D. // PLoS ONE;Dec2013, Vol. 8 Issue 12, p1 

    Telomeres are specialized chromatin structures found at the end of chromosomes and are crucial to the maintenance of eukaryotic genome stability. Human telomere DNA is comprised of the repeating sequence (T2AG3)n, which is predominantly double-stranded but terminates with a 3’...

  • Antitumor activity of G-quadruplex-interactive agent TMPyP4 with photodynamic therapy in ovarian carcinoma cells. HONGLI LIU; CHANGSHUAI LV; BAIJUAN DING; JIE WANG; SHAN LI; YOUZHONG ZHANG // Oncology Letters;2014, Vol. 8 Issue 1, p409 

    The aim of the present study was to investigate the potential effects of photodynamic therapy (PDT) mediated by the cationic porphyrin, 5,10,15,20-tetra-(N-methyl- 4-pyridyl)porphine (TMPyP4), on an ovarian carcinoma cell line and the underlying mechanisms by which TMPyP4-PDT exerts its actions....

  • Binding of Gemini Bisbenzimidazole Drugs with Human Telomeric G-Quadruplex Dimers: Effect of the Spacer in the Design of Potent Telomerase Inhibitors. Paul, Ananya; Jain, Akash K.; Misra, Santosh K.; Maji, Basudeb; Muniyappa, K.; Bhattacharya, Santanu // PLoS ONE;Jun2012, Vol. 7 Issue 6, p1 

    The study of anticancer agents that act via stabilization of telomeric G-quadruplex DNA (G4DNA) is important because such agents often inhibit telomerase activity. Several types of G4DNA binding ligands are known. In these studies, the target structures often involve a single G4 DNA unit formed...

  • Targeting Human Telomeric G-Quadruplex DNA and Inhibition of Telomerase Activity With [(dmb)2Ru(obip)Ru(dmb)2]4+. Shi, Shuo; Gao, Shane; Cao, Tongcheng; Liu, Jie; Gao, Xing; Hao, Jian; Lv, Chunyan; Huang, Hailiang; Xu, Jun; Yao, Tianming // PLoS ONE;Dec2013, Vol. 8 Issue 12, p1 

    Inhibition of telomerase by inducing/stabilizing G-quadruplex formation is a promising strategy to design new anticancer drugs. We synthesized and characterized a new dinuclear complex [(dmb)2Ru(obip)Ru(dmb)2]4+ (dmb = 4,4’-dimethyl-2,2’-bipyridine, obip =...

  • Small-molecule-induced DNA damage identifies alternative DNA structures in human genes. Rodriguez, Raphaël; Miller, Kyle M; Forment, Josep V; Bradshaw, Charles R; Nikan, Mehran; Britton, Sébastien; Oelschlaegel, Tobias; Xhemalce, Blerta; Balasubramanian, Shankar; Jackson, Stephen P // Nature Chemical Biology;Mar2012, Vol. 8 Issue 3, p301 

    Guanine-rich DNA sequences that can adopt non-Watson-Crick structures in vitro are prevalent in the human genome. Whether such structures normally exist in mammalian cells has, however, been the subject of active research for decades. Here we show that the G-quadruplex-interacting drug...

  • Selective Binding of Distamycin A Derivative to G-Quadruplex Structure [d(TGGGGT)]4. Pagano, Bruno; Fotticchia, Iolanda; De Tito, Stefano; Mattia, Carlo A.; Mayol, Luciano; Novellino, Ettore; Randazzo, Antonio; Giancola, Concetta // Journal of Nucleic Acids;2010, p1 

    Guanine-rich nucleic acid sequences can adopt G-quadruplex structures stabilized by layers of four Hoogsteen-paired guanine residues. Quadruplex-prone sequences are found in many regions of human genome and in the telomeres of all eukaryotic organisms. Since small molecules that target...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics