Monomolecular G-quadruplex Structures with Inversion of Polarity Sites: New Topologies and Potentiality

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2017 Jul 2

PMID 28666330

Citations 5

Authors

Antonella Virgilio

Annapina Russo

Teresa Amato

Giulia Russo

Luciano Mayol

Veronica Esposito

Aldo Galeone

Affiliations

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Abstract

In this paper, we report investigations, based on circular dichroism, nuclear magnetic resonance spectroscopy and electrophoresis methods, on three oligonucleotide sequences, each containing one 3'-3' and two 5'-5' inversion of polarity sites, and four G-runs with a variable number of residues, namely two, three and four (mTG2T, mTG3T and mTG4T with sequence 3'-TGnT-5'-5'-TGnT-3'-3'-TGnT-5'-5'-TGnT-3' in which n = 2, 3 and 4, respectively), in comparison with their canonical counterparts (TGnT)4 (n = 2, 3 and 4). Oligonucleotides mTG3T and mTG4T have been proven to form very stable unprecedented monomolecular parallel G-quadruplex structures, characterized by three side loops containing the inversion of polarity sites. Both G-quadruplexes have shown an all-syn G-tetrad, while the other guanosines adopt anti glycosidic conformations. All oligonucleotides investigated have shown a noteworthy antiproliferative activity against lung cancer cell line Calu 6 and colorectal cancer cell line HCT-116 p53-/-. Interestingly, mTG3T and mTG4T have proven to be mostly resistant to nucleases in a fetal bovine serum assay. The whole of the data suggest the involvement of specific pathways and targets for the biological activity.

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References

Virgilio A, Esposito V, Citarella G, Mayol L, Galeone A . Structural investigations on the anti-HIV G-quadruplex-forming oligonucleotide TGGGAG and its analogues: evidence for the presence of an A-tetrad. Chembiochem. 2012; 13(15):2219-24. DOI: 10.1002/cbic.201200481. View

Varizhuk A, Ilyinsky N, Smirnov I, Pozmogova G . G4 Aptamers: Trends in Structural Design. Mini Rev Med Chem. 2016; 16(16):1321-1329. DOI: 10.2174/1389557516666160321114715. View

Jin R, Gaffney B, Wang C, Jones R, Breslauer K . Thermodynamics and structure of a DNA tetraplex: a spectroscopic and calorimetric study of the tetramolecular complexes of d(TG3T) and d(TG3T2G3T). Proc Natl Acad Sci U S A. 1992; 89(18):8832-6. PMC: 50015. DOI: 10.1073/pnas.89.18.8832. View

Tran P, Virgilio A, Esposito V, Citarella G, Mergny J, Galeone A . Effects of 8-methylguanine on structure, stability and kinetics of formation of tetramolecular quadruplexes. Biochimie. 2010; 93(3):399-408. DOI: 10.1016/j.biochi.2010.10.011. View

Feigon J, Koshlap K, Smith F . 1H NMR spectroscopy of DNA triplexes and quadruplexes. Methods Enzymol. 1995; 261:225-55. DOI: 10.1016/s0076-6879(95)61012-x. View

Virgilio A, Amato T, Petraccone L, Filosa R, Varra M, Mayol L . Improved thrombin binding aptamer analogues containing inversion of polarity sites: structural effects of extra-residues at the ends. Org Biomol Chem. 2016; 14(32):7707-14. DOI: 10.1039/c6ob00931j. View

Teng Y, Girvan A, Casson L, Pierce Jr W, Qian M, Thomas S . AS1411 alters the localization of a complex containing protein arginine methyltransferase 5 and nucleolin. Cancer Res. 2007; 67(21):10491-500. DOI: 10.1158/0008-5472.CAN-06-4206. View

Vorlickova M, Kejnovska I, Sagi J, Renciuk D, Bednarova K, Motlova J . Circular dichroism and guanine quadruplexes. Methods. 2012; 57(1):64-75. DOI: 10.1016/j.ymeth.2012.03.011. View

Russo A, Pagliara V, Albano F, Esposito D, Sagar V, Loreni F . Regulatory role of rpL3 in cell response to nucleolar stress induced by Act D in tumor cells lacking functional p53. Cell Cycle. 2015; 15(1):41-51. PMC: 4825706. DOI: 10.1080/15384101.2015.1120926. View

10.

Zhang N, Bing T, Liu X, Qi C, Shen L, Wang L . Cytotoxicity of guanine-based degradation products contributes to the antiproliferative activity of guanine-rich oligonucleotides. Chem Sci. 2017; 6(7):3831-3838. PMC: 5707456. DOI: 10.1039/c4sc03949a. View

11.

Sagi J . G-quadruplexes incorporating modified constituents: a review. J Biomol Struct Dyn. 2013; 32(3):477-511. DOI: 10.1080/07391102.2013.775074. View

12.

Esposito D, Crescenzi E, Sagar V, Loreni F, Russo A, Russo G . Human rpL3 plays a crucial role in cell response to nucleolar stress induced by 5-FU and L-OHP. Oncotarget. 2014; 5(22):11737-51. PMC: 4294388. DOI: 10.18632/oncotarget.2591. View

13.

Lago S, Tosoni E, Nadai M, Palumbo M, Richter S . The cellular protein nucleolin preferentially binds long-looped G-quadruplex nucleic acids. Biochim Biophys Acta Gen Subj. 2016; 1861(5 Pt B):1371-1381. PMC: 5466061. DOI: 10.1016/j.bbagen.2016.11.036. View

14.

Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, Brown J . Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science. 1998; 282(5393):1497-501. DOI: 10.1126/science.282.5393.1497. View

15.

Esposito V, Russo A, Amato T, Varra M, Vellecco V, Bucci M . Backbone modified TBA analogues endowed with antiproliferative activity. Biochim Biophys Acta Gen Subj. 2016; 1861(5 Pt B):1213-1221. DOI: 10.1016/j.bbagen.2016.09.019. View

16.

Oliviero G, Borbone N, Amato J, DErrico S, Galeone A, Piccialli G . Synthesis of quadruplex-forming tetra-end-linked oligonucleotides: effects of the linker size on quadruplex topology and stability. Biopolymers. 2009; 91(6):466-77. DOI: 10.1002/bip.21153. View

17.

Juskowiak B . Analytical potential of the quadruplex DNA-based FRET probes. Anal Chim Acta. 2007; 568(1-2):171-80. DOI: 10.1016/j.aca.2005.12.063. View

18.

Oliviero G, Amato J, Borbone N, DErrico S, Galeone A, Mayol L . Tetra-end-linked oligonucleotides forming DNA G-quadruplexes: a new class of aptamers showing anti-HIV activity. Chem Commun (Camb). 2010; 46(47):8971-3. DOI: 10.1039/c0cc02866e. View

19.

Masiero S, Trotta R, Pieraccini S, De Tito S, Perone R, Randazzo A . A non-empirical chromophoric interpretation of CD spectra of DNA G-quadruplex structures. Org Biomol Chem. 2010; 8(12):2683-92. DOI: 10.1039/c003428b. View

20.

Wyatt J, Davis P, Freier S . Kinetics of G-quartet-mediated tetramer formation. Biochemistry. 1996; 35(24):8002-8. DOI: 10.1021/bi960124h. View