PNA Oligomers as Tools for Targeting G-Quadruplex Structures

Jussara Amato(1*)

(1) Dipartimento di Chimica delle Sostanze Naturali, Università degli Studi di Napoli “Federico II”, via D. Montesano 49, 80131, Napoli, Italy
(*) Corresponding author

DOI's assignment:
the author of the article can submit here a request for assignment of a DOI number to this resource!
Cost of the service: euros 10,00 (for a DOI)


G-quadruplex-forming sequences (QFS) are widely distributed in the human genome, including chromosomal telomeres and regulatory regions of oncogenes, and are involved in a variety of biological contexts. Molecular probes that selectively target QFS have been investigated to delineate their biological role and to identify potential therapeutic agents. Peptide nucleic acids (PNAs) targeting to QFS can be designed using two different approaches. In the first, complementary cytosine-rich PNAs can hybridize to the target QFS by forming PNA:DNA or PNA:RNA hybrid duplexes. In the second, guanine-rich PNAs can hybridize to the homologous DNA or RNA target by forming the corresponding heteroquadruplexes. This review discusses the principles and the recent improvements of the complementary and homologous hybridization modes of PNA oligomers
Copyright © 2011 Praise Worthy Prize - All rights reserved.


G-Quadruplex; Peptide Nucleic Acid (PNA); Hybridization

Full Text:



A.T. Phan, Human telomeric G-quadruplex: structures of DNA and RNA sequences, FEBS Journal, Volume 277, (Issue 5), March 2010, Pages 1107-1117.

M.A. Keniry, Quadruplex structures in nucleic acids, Biopolymers, Volume 56, (Issue 3), 2001, Pages 123–146.

D.J. Patel, A.T. Phan, V. Kuryavyi, Human telomere, oncogenic promoter and 5′-UTR G-quadruplexes: diverse higher order DNA and RNA targets for cancer therapeutics, Nucleic Acids Research, Volume 35, (Issue 22), October 2007, Pages 7429-7455.

L. Martino, B. Pagano, I. Fotticchia, S. Neidle, C. Giancola, Shedding light on the interaction between TMPyP4 and human telomeric quadruplexes, Journal of Physical Chemistry B, Volume 113, (Issue 44), November 2009, Pages 14779-14786.

B. Pagano, I. Fotticchia, S. De Tito, C.A. Mattia, L. Mayol, E. Novellino, A. Randazzo, C. Giancola, Selective Binding of Distamycin A Derivative to G-Quadruplex Structure [d(TGGGGT)]4, Journal of Nucleic Acids, Volume 2010, May 2010, Article ID 247137, 7 Pages.

L. Petraccone, I. Fotticchia, A. Cummaro, B. Pagano, L. Ginnari-Satriani, S. Haider, A. Randazzo, E. Novellino, S. Neidle, C. Giancola, The triazatruxene derivative azatrux binds to the parallel form of the human telomeric G-quadruplex under molecular crowding conditions: Biophysical and molecular modeling studies, Biochimie., Volume 93, (Issue 8), August 2011, Pages 1318-1327.

B. Datta, B.A. Armitage, Hybridization of PNA to structured DNA targets: quadruplex invasion and the overhang effect, Journal of the American Chemical Society, Volume 123, (Issue 39), October 2001, Pages 9612-9619.

J.J Green, L. Ying, D. Klenerman, S. Balasubramanian, Kinetics of unfolding the human telomeric DNA quadruplex using a PNA trap. Journal of the American Chemical Society, Volume 125, (Issue 13), April 2003, Pages 3763-3767.

N. Kumar, A. Patowary, S. Sivasubbu, M. Petersen, S. Maiti, Silencing c-MYC expression by targeting quadruplex in P1 promoter using locked nucleic acid trap, Biochemistry, Volume 47, (Issue 50), December 2008, Pages 13179-13188.

J. Amato, G. Oliviero, E. De Pauw, V. Gabelica, Hybridization of short complementary PNAs to G-quadruplex forming oligonucleotides: An electrospray mass spectrometry study, Biopolymers, Volume 91, (Issue 4), April 2009, Pages 244-255.

P.E. Nielsen, M. Egholm, R.H. Berg, O. Buchardt, Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide, Science, December 1991, Volume 254, (Issue 5037), Pages 1497-1500.

M. Egholm, O. Buchardt, L. Christensen, C. Behrens, S.M. Freier, D.A. Driver, R.H. Berg, S.K. Kim, B. Norden, P.E. Nielsen, PNA hybridizes to complementary oligonucleotides obeying the Watson-Crick hydrogen-bonding rules, Nature, Volume 365, (Issue 6446), October 1993, Pages 566-568.

D. Jakimov, D. Cetojevic-Simin, V. Kojic, J. Mrdanovic, Peptide Nucleic Acid (PNA) - more than anyone could imagine at the first sight, Archive of Oncology, Volume 8, (Issue 1), January 2000, Pages 11-14.

B. Datta, M.E. Bier, S. Roy, B.A. Armitage, Quadruplex formation by a guanine-rich PNA oligomer, Journal of the American Chemical Society, Volume 127, (Issue 12), March 2005, Pages 4199-4207.

V.L. Marin, B.A. Armitage, Hybridization of complementary and homologous peptide nucleic acid oligomers to a guanine quadruplex-forming RNA, Biochemistry, Volume 45, (Issue 6), February 2006, Pages 1745-1754.

B. Datta, C. Schmitt, B.A. Armitage, Formation of a PNA2−DNA2 hybrid quadruplex, Journal of the American Chemical Society, Volume 125, (Issue 14), April 2003, Pages 4111–4118.

J.R. Williamson, M.K. Raghuraman, T.R. Cech, Monovalent cation-induced structure of telomeric DNA: the G-quartet model, Cell, Volume 59, (Issue 5), December 1989, Pages 871-880.

S. Lusvarghi, C.T. Murphy, S. Roy, F.A. Tanious, I. Sacui, W.D. Wilson, D.H. Ly, B.A. Armitage, Loop and backbone modifications of PNA improve G-quadruplex binding selectivity, Journal of the American Chemical Society, Volume 131, (Issue 51), December 2009, Pages 18415–18424.

I.V. Smolina, V.V. Demidov, V.A. Soldatenkov, S.G Chasovskikh, M.D. Frank-Kamenetskii, End invasion of peptide nucleic acids (PNAs) with mixed-base composition into linear DNA duplexes, Nucleic Acids Research, Volume 33, (Issue 17), October 2005, Pages e146.

F. Totsingan, S. Rossi, R. Corradini, T. Tedeschi, S. Sforza, A. Juris, E. Scaravelli, R. Marchelli, Label-free selective DNA detection with high mismatch recognition by PNA beacons and ion exchange HPLC, Organic and Biomolecular Chemistry, Volume 6, (Issue 7), April 2008, Pages 1232-1237.

N. Rufer, W. Dragowska, G. Thornbury, E. Roosnek, P.M. Lansdorp, Telomere length dynamics in human lymphocyte subpopulations measured by flow cytometry, Nature Biotechnology, Volume 16, (Issue 8), August 1998, Pages 743-747.

J. Feng, W.D. Funk, S.S. Wang, S.L. Weinrich, A.A. Avilion, C.P. Chiu, R.R. Adams, E. Chang, R.C. Allsopp, J.H. Yu, et al., The RNA component of human telomerase, Science, Volume 269, September 1995, Pages 1236–1241.

S.E. Hamilton, A.E. Pitts, R.R. Katipally, X. Jia, J.P. Rutter, B.A. Davies, J.W. Shay, W.E. Wright, D.R. Corey, Identification of determinants for inhibitor binding within the RNA active site of human telomerase using PNA scanning, Biochemistry, Volume 36, (Issue 39), September 1997, Pages 11873-11880.

A.E. Pitts, D.R. Corey, Inhibition of human telomerase by 2'-O-methyl-RNA, Proceedings of the National Academy of Sciences USA, Volume 95, (Issue 20), September 1998, Pages 11549-11554.

J.G. Harrison, C. Frier, R. Laurant, R. Dennis, K.D. Raney, S. Balasubramanian, Inhibition of human telomerase by PNA-cationic peptide conjugates, Bioorganic and Medicinal Chemistry Letters, Volume 9, (Issue 9), May 1999, Pages 1273-1278.

S.E. Hamilton, C.G. Simmons, I.S. Kathiriya, D.R. Corey, Cellular delivery of peptide nucleic acids and inhibition of human telomerase, Chemical Biology, Volume 6, (Issue 6), June 1999, Pages 343-351.

R. Villa, M. Folini, S. Lualdi, S. Veronese, M.G. Daidone, N. Zaffaroni, Inhibition of telomerase activity by a cell-penetrating peptide nucleic acid construct in human melanoma cells, FEBS Letters, Volume 473,(Issue 2), May 2000, Pages 241-248.

V.V. Demidov, E. Protozanova, K.I. Izvolsky, C. Price, P.E. Nielsen, M.D. Frank-Kamenetskii, Kinetics and mechanism of the DNA double helix invasion by pseudocomplementary peptide nucleic acids, Proceedings of the National Academy of Sciences USA, Volume 99, (Issue 9), April 2002, Pages 5953-5958.

P.E. Nielsen, M. Egholm, O. Buchardt, Evidence for (PNA)2/DNA triplex structure upon binding of PNA to dsDNA by strand displacement, Journal Molecular Recognition, Volume 7, (Issue 3), September 1994, Pages 165-70.

J.A. Kelly, J. Feigon, T.O. Yeates, Reconciliation of the X-ray and NMR structures of the thrombin-binding aptamer d(GGTTGGTGTGGTTGG), Journal Molecular Biology, Volume 256, (Issue 3), March 1996, Pages 417-422.

J.J. Green, L. Ying, D. Klenerman, S. Balasubramanian, Kinetics of unfolding the human telomeric DNA quadruplex using a PNA trap, Journal of American Chemical Society, Volume 125, (Issue 13), April 2003, Pages 3763-3767.

A. Ramos, D. Hollingworth, A. Pastore, G-quartet-dependent recognition between the FMRP RGG box and RNA, RNA, Volume 9, (Issue 10), October 2003, Pages 1198-1207.

B.A. Armitage, The impact of nucleic acid secondary structure on PNA hybridization, Drug Discovery Today, Volume 8, (Issue 5), March 2003, Pages 222-228.

J. Amato, B. Pagano, N. Borbone, G. Oliviero, V. Gabelica, De Pauw E., S. D'Errico, V. Piccialli, M. Varra, C. Giancola, G. Piccialli, L. Mayol, Targeting G-quadruplex structure in the human c-Kit promoter with short PNA sequences, Bioconjugate Chemistry, Volume 22,(Issue 4), April 2011, Pages 654-663.

S. Roy, F.A. Tanious, W.D. Wilson, D.H. Ly, B.A. Armitage, High-affinity homologous peptide nucleic acid probes for targeting a quadruplex-forming sequence from a MYC promoter element, Biochemistry, Volume 46, (Issue 37), September 2007, Pages 10433-10443.

L. Petraccone, B. Pagano, V. Esposito, A. Randazzo, G. Piccialli, G. Barone, C.A. Mattia, C. Giancola, Thermodynamics and Kinetics of PNA-DNA Quadruplex-Forming Chimeras, Journal of American Chemical Society, Volume 127, (Issue 46), November 2005, Pages 16215-16223.

Y. Krishnan-Ghosh, E. Stephens, S. Balasubramanian, A PNA4 quadruplex, Journal of American Chemical Society, Volume 126, (Issue 119), May 2004, Pages 5944-5945.

S. Saha, J. Cai, D. Eiler, A.D. Hamilton, Programming the formation of DNA and PNA quadruplexes by pi-pi-stacking interactions, Chemical Communication, Volume 46, (Issue 10), March 2010, Pages 1685-1687.

M.I. Onyshchenko, T.I. Gaynutdinov, E.A. Englund, D.H. Appella, R.D. Neumann, I.G. Panyutin, Stabilization of G-quadruplex in the BCL2 promoter region in double-stranded DNA by invading short PNAs, Nucleic Acids Research, Volume 37, (Issue 22), December 2009, Pages 7570-7580.

S. Roy, K.J. Zanotti, C.T. Murphy, F.A. Tanious, W.D. Wilson, D.H. Ly, B.A. Armitage, Kinetic discrimination in recognition of DNA quadruplex targets by guanine-rich heteroquadruplex-forming PNA probes, Chemical Communication, Volume 47, (Issue 30), August 2011, Pages 8524-8526.


  • There are currently no refbacks.

Please send any question about this web site to
Copyright © 2005-2019 Praise Worthy Prize