Skip to main content
SpringerLink
Log in

Energetics of Ligand Binding to G-Quadruplexes

  • Chapter
  • First Online:
Quadruplex Nucleic Acids

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 330))

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Blackburn EH (1991) Structure and function of telomeres. Nature 350:569–573

    Article  CAS  Google Scholar 

  2. de Lange T (2005) Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev 19:2100–2110

    Article  Google Scholar 

  3. Shay J, Wright W (2006) Telomerase therapeutics for cancer: challenges and new directions. Nat Rev Drug Discov 5:577–584

    Article  CAS  Google Scholar 

  4. Zahler AM, Williamson JR, Cech TR et al (1991) Inhibition of telomerase by G-quartet DNA structures. Nature 350:718–720

    Article  CAS  Google Scholar 

  5. Blackburn EH (1992) Telomerases. Annu Rev Biochem 61:113–129

    Article  CAS  Google Scholar 

  6. Kim NW, Piatyszek MA, Prowse KR et al (1994) Specific association of human telomerase activity with immortal cells and cancer. Science 266:2011–2015

    Article  CAS  Google Scholar 

  7. De Cian A, Lacroix L, Douarre C et al (2008) Targeting telomeres and telomerase. Biochimie 90:131–155

    Article  Google Scholar 

  8. Neidle S (2010) Human telomeric G-quadruplex: the current status of telomeric G-quadruplexes as therapeutic targets in human cancer. FEBS J 277:1118–1125

    Article  CAS  Google Scholar 

  9. Freire E (2008) Do enthalpy and entropy distinguish first in class from best in class? Drug Discov Today 13:869–874

    Article  CAS  Google Scholar 

  10. Ladbury JE, Klebe G, Freire E (2010) Adding calorimetric data to decision making in lead discovery: a hot tip. Nat Rev Drug Discov 9:23–27

    Article  CAS  Google Scholar 

  11. Meanwell NA (2011) Improving drug candidates by design: a focus on physicochemical properties as a means of improving compound disposition and safety. Chem Res Toxicol 24:1420–1456

    Article  CAS  Google Scholar 

  12. Doyle ML (1997) Characterization of binding interactions by isothermal titration calorimetry. Curr Opin Biotechnol 8:31–35

    Article  CAS  Google Scholar 

  13. Ababou A, Ladbury JE (2007) Survey of the year 2005: literature on applications of isothermal titration calorimetry. J Mol Recognit 20:4–14

    Article  CAS  Google Scholar 

  14. Pagano B, Mattia CA, Giancola C (2009) Applications of isothermal titration calorimetry in biophysical studies of G-quadruplexes. Int J Mol Sci 10:2935–2957

    Article  CAS  Google Scholar 

  15. Pagano B, Giancola C (2007) Energetics of quadruplex-drug recognition in anticancer therapy. Curr Cancer Drug Targets 7:520–540

    Article  CAS  Google Scholar 

  16. Martino L, Pagano B, Fotticchia I et al (2009) Shedding light on the interaction between TMPyP4 and human telomeric quadruplexes. J Phys Chem B 113:14779–14786

    Article  CAS  Google Scholar 

  17. Peng D, Tan JH, Chen SB et al (2010) Bisaryldiketene derivatives: a new class of selective ligands for c-myc G-quadruplex DNA. Bioorg Med Chem 18:8235–8242

    Article  CAS  Google Scholar 

  18. Bhadra K, Kumar GS (2011) Interaction of berberine, palmatine, coralyne, and sanguinarine to quadruplex DNA: a comparative spectroscopic and calorimetric study. Biochim Biophys Acta 1810:485–496

    Article  CAS  Google Scholar 

  19. Chaires JB (2008) Calorimetry and thermodynamics in drug design. Annu Rev Biophys 37:135–151

    Article  CAS  Google Scholar 

  20. Leavitt S, Freire E (2001) Direct measurement of protein binding energetics by isothermal titration calorimetry. Curr Opin Struct Biol 11:560–566

    Article  CAS  Google Scholar 

  21. Brown A (2009) Analysis of cooperativity by isothermal titration calorimetry. Int J Mol Sci 10:3457–3477

    Article  CAS  Google Scholar 

  22. LaKowicz JR (2006) Principles of fluorescence spectroscopy, vol 1, 3rd edn. Springer, New York, 954 p

    Book  Google Scholar 

  23. Miannay FA, Banyasz A, Gustavsson T et al (2009) Excited states and energy transfer in G-quadruplexes. J Phys Chem C 113:11760–11765

    Article  CAS  Google Scholar 

  24. Mendez MA, Szalai VA (2009) Fluorescence of unmodified oligonucleotides: a tool to probe G-quadruplex DNA structure. Biopolymers 91:841–850

    Article  CAS  Google Scholar 

  25. Dao NT, Haselsberger R, Michel-Beyerle ME et al (2011) Following G-quadruplex formation by its intrinsic fluorescence. FEBS Lett 585:3969–3977

    Article  Google Scholar 

  26. Chang CC, Chien CW, Lin YH et al (2007) Investigation of spectral conversion of d(TTAGGG)4 and d(TTAGGG)13 upon potassium titration by a G-quadruplex recognizer BMVC molecule. Nucleic Acids Res 35:2846–2860

    Article  CAS  Google Scholar 

  27. Cummaro A, Fotticchia I, Franceschin M et al (2011) Binding properties of human telomeric quadruplex multimers: a new route for drug design. Biochimie 93:1392–1400

    Article  CAS  Google Scholar 

  28. Petraccone L, Fotticchia I, Cummaro A et al (2011) 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 93:1318–1327

    Article  CAS  Google Scholar 

  29. Monchaud D, Allain C, Teulade-Fichou MP (2006) Development of a fluorescent intercalator displacement assay (G4-FID) for establishing quadruplex-DNA affinity and selectivity of putative ligands. Bioorg Med Chem Lett 16:4842–4845

    Article  CAS  Google Scholar 

  30. Monchaud D, Allain C, Bertrand H et al (2008) Ligands playing musical chairs with G-quadruplex DNA: a rapid and simple displacement assay for identifying selective G-quadruplex binders. Biochimie 90:1207–1223

    Article  CAS  Google Scholar 

  31. Förster T (1948) Zwischenmolekulare Energiewanderung und Fluoreszenz. Ann Phys 437:55–75

    Article  Google Scholar 

  32. Mergny JL, Maurizot JC (2001) Fluorescence resonance energy transfer as a probe for G-quartet formation by a telomeric repeat. Chembiochem 2:124–132

    Article  CAS  Google Scholar 

  33. De Cian A, Guittat L, Kaiser M et al (2007) Fluorescence-based melting assays for studying quadruplex ligands. Methods 42:183–195

    Article  Google Scholar 

  34. Juskowiak B (2006) Analytical potential of the quadruplex DNA-based FRET probes. Anal Chim Acta 568:171–180

    Article  CAS  Google Scholar 

  35. Fasman GD (1996) Circular dichroism and the conformational analysis of biomolecules. Plenum Press, New York

    Book  Google Scholar 

  36. Masiero S, Trotta R, Pieraccini S et al (2010) A non-empirical chromophoric interpretation of CD spectra of DNA G-quadruplex structures. Org Biomol Chem 8:2683–2692

    Article  CAS  Google Scholar 

  37. Karsisiotis AI, Hessari NM, Novellino E et al (2011) Topological characterization of nucleic acid G-quadruplexes by UV absorption and circular dichroism. Angew Chem Int Ed Engl 50:10645–10648

    Article  CAS  Google Scholar 

  38. Li W, Wu P, Ohmichi T et al (2002) Characterization and thermodynamic properties of quadruplex/duplex competition. FEBS Lett 526:77–81

    Article  CAS  Google Scholar 

  39. Li J, Correia JJ, Wang L et al (2005) Not so crystal clear: the structure of the human telomere G-quadruplex in solution differs from that present in a crystal. Nucleic Acids Res 33:4649–4659

    Article  CAS  Google Scholar 

  40. Balagurumoorthy P, Brahmachari SK, Mohanty D et al (1992) Hairpin and parallel quartet structures for telomeric sequences. Nucleic Acids Res 20:4061–4067

    Article  CAS  Google Scholar 

  41. Jin R, Gaffney BL, Wang C et al (1992) 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 USA 89:8832–8836

    Article  CAS  Google Scholar 

  42. Lu M, Guo Q, Kallenbach NR (1993) Thermodynamics of G-tetraplex formation by telomeric DNAs. Biochemistry 32:598–601

    Article  CAS  Google Scholar 

  43. Sun H, Tang Y, Xiang J et al (2006) Spectroscopic studies of the interaction between quercetin and G-quadruplex DNA. Bioorg Med Chem Lett 16:3586–3589

    Article  CAS  Google Scholar 

  44. Garbett NC, Ragazzon PA, Chaires JB (2007) Circular dichroism to determine binding mode and affinity of ligand-DNA interactions. Nat Protoc 2:3166–3172

    Article  CAS  Google Scholar 

  45. Hudson JS, Brooks SC, Graves DE (2009) Interactions of actinomycin D with human telomeric G-quadruplex DNA. Biochemistry 48:4440–4447

    Article  CAS  Google Scholar 

  46. Arora A, Balasubramanian C, Kumar N et al (2008) Binding of berberine to human telomeric quadruplex – spectroscopic, calorimetric and molecular modeling studies. FEBS J 275:3971–3983

    Article  CAS  Google Scholar 

  47. Chen Z, Zheng KW, Hao YH et al (2009) Reduced or diminished stabilization of the telomere G-quadruplex and inhibition of telomerase by small chemical ligands under molecular crowding condition. J Am Chem Soc 131:10430–10438

    Article  CAS  Google Scholar 

  48. Chaires JB (2006) A thermodynamic signature for drug-DNA binding mode. Arch Biochem Biophys 453:26–31

    Article  CAS  Google Scholar 

  49. Zhang HJ, Wang XF, Wang P et al (2008) Spectroscopic study on the binding of a cationic porphyrin to DNA G-quadruplex under different K+ concentrations. Photochem Photobiol Sci 7:948–955

    Article  CAS  Google Scholar 

  50. Wheelhouse RT, Sun D, Han H et al (1998) Cationic porphyrins as telomerase inhibitors: the interaction of tetra-(N-methyl-4-pyridyl)porphine with quadruplex DNA. J Am Chem Soc 120:3261–3262

    Article  CAS  Google Scholar 

  51. Siddiqui-Jain A, Grand CL, Bearss DJ et al (2002) Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c-MYC transcription. Proc Natl Acad Sci USA 99:11593–11598

    Article  CAS  Google Scholar 

  52. Haq I, Trent JO, Chowdhry BZ et al (1999) Intercalative G-tetraplex stabilization of telomeric DNA by a cationic porphyrin. J Am Chem Soc 121:1768–1779

    Article  CAS  Google Scholar 

  53. Han FXG, Wheelhouse RT, Hurley LH (1999) Cationic porphyrins as telomerase inhibitors: the interaction of tetra (N-methyl-4-pyridyl) porphyrin with quadruplex DNA. J Am Chem Soc 121:3561–3570

    Article  CAS  Google Scholar 

  54. Han H, Langley DR, Rangan A et al (2001) Selective interactions of cationic porphyrins with G-quadruplex structures. J Am Chem Soc 123:8902–8913

    Article  CAS  Google Scholar 

  55. Erra E, Petraccone L, Esposito V et al (2005) Interaction of porphyrin with G-quadruplex structures. Nucleosides Nucleotides Nucleic Acids 24:753–756

    Article  CAS  Google Scholar 

  56. Phan AT, Kuryavyi V, Gaw HY et al (2005) Small-molecule interaction with a five-guanine-tract G-quadruplex structure from the human MYC promoter. Nat Chem Biol 1:167–173

    Article  CAS  Google Scholar 

  57. Wei C, Jia G, Yuan J et al (2006) A spectroscopic study on the interactions of porphyrin with G-quadruplex DNAs. Biochemistry 45:6681–6691

    Article  CAS  Google Scholar 

  58. Parkinson GN, Ghosh R, Neidle S (2007) Structural basis for binding of porphyrin to human telomeres. Biochemistry 46:2390–2397

    Article  CAS  Google Scholar 

  59. Gaynutdinov TI, Neumann RD, Panyutin IG (2008) Structural polymorphism of intramolecular quadruplex of human telomeric DNA: effect of cations, quadruplex-binding drugs and flanking sequences. Nucleic Acids Res 36:4079–4087

    Article  CAS  Google Scholar 

  60. Arora A, Maiti S (2008) Effect of loop orientation on quadruplex-TMPyP4 interaction. J Phys Chem B 112:8151–8159

    Article  CAS  Google Scholar 

  61. Pagano B, Virno A, Mattia CA et al (2008) Targeting DNA quadruplexes with distamycin A and its derivatives: an ITC and NMR study. Biochimie 90:1224–1232

    Article  CAS  Google Scholar 

  62. Gray RD, Li J, Chaires JB (2009) Energetics and kinetics of a conformational switch in G-quadruplex DNA. J Phys Chem B 113:2676–2683

    Article  CAS  Google Scholar 

  63. Xue Y, Kan ZY, Wang Q et al (2007) Human telomeric DNA forms parallel-stranded intramolecular G-quadruplex in K+ solution under molecular crowding condition. J Am Chem Soc 129:11185–11191

    Article  CAS  Google Scholar 

  64. Parkinson GN, Lee MP, Neidle S (2002) Crystal structure of parallel quadruplexes from human telomeric DNA. Nature 417:876–880

    Article  CAS  Google Scholar 

  65. Zhou HX, Rivas G, Minton AP (2008) Macromolecular crowding and confinement: biochemical, biophysical, and potential physiological consequences. Annu Rev Biophys 37:375–397

    Article  CAS  Google Scholar 

  66. Miller MC, Buscaglia R, Chaires JB et al (2010) Hydration is a major determinant of the G-quadruplex stability and conformation of the human telomere 3′ sequence of d[AG3(TTAG3)3]. J Am Chem Soc 132:17105–17107

    Article  CAS  Google Scholar 

  67. Hansel R, Lohr F, Foldynova-Trantirkova S et al (2011) The parallel G-quadruplex structure of vertebrate telomeric repeat sequences is not the preferred folding topology under physiological conditions. Nucleic Acids Res 39:5768–5775

    Article  Google Scholar 

  68. Petraccone L, Pagano B, Giancola C (2012) Studying the effect of crowding and dehydration on DNA G-quadruplexes. Methods. doi:10.1016/j.ymeth.2012.02.011

  69. Wei C, Jia G, Zhou J et al (2009) Evidence for the binding mode of porphyrins to G-quadruplex DNA. Phys Chem Chem Phys 11:4025–4032

    Article  CAS  Google Scholar 

  70. Phan AT, Luu KN, Patel DJ (2006) Different loop arrangements of intramolecular human telomeric (3+1) G-quadruplexes in K+ solution. Nucleic Acids Res 34:5715–5719

    Article  CAS  Google Scholar 

  71. Dai J, Carver M, Punchihewa C et al (2007) Structure of the Hybrid-2 type intramolecular human telomeric G-quadruplex in K+ solution: insights into structure polymorphism of the human telomeric sequence. Nucleic Acids Res 35:4927–4940

    Article  CAS  Google Scholar 

  72. Dai J, Punchihewa C, Ambrus A et al (2007) Structure of the intramolecular human telomeric G-quadruplex in potassium solution: a novel adenine triple formation. Nucleic Acids Res 35:2440–2450

    Article  CAS  Google Scholar 

  73. Bhattacharjee AJ, Ahluwalia K, Taylor S et al (2011) Induction of G-quadruplex DNA structure by Zn(II) 5,10,15,20-tetrakis (N-methyl-4-pyridyl)porphyrin. Biochimie 93:1297–1309

    Article  CAS  Google Scholar 

  74. Pan J, Zhang S (2009) Interaction between cationic zinc porphyrin and lead ion induced telomeric guanine quadruplexes: evidence for end-stacking. J Biol Inorg Chem 14:401–407

    Article  CAS  Google Scholar 

  75. Ginnari-Satriani L, Casagrande V, Bianco A et al (2009) A hydrophilic three side-chained triazatruxene as a new strong and selective G-quadruplex ligand. Org Biomol Chem 7:2513–2516

    Article  CAS  Google Scholar 

  76. Todd AK, Haider SM, Parkinson GN et al (2007) Sequence occurrence and structural uniqueness of a G-quadruplex in the human c-kit promoter. Nucleic Acids Res 35:5799–5808

    Article  CAS  Google Scholar 

  77. Thomas M, Varshney U, Bhattacharya S (2002) Distamycin analogs without leading amide at the N-terminus: comparative binding properties to AT and GC rich DNA sequences. Eur J Org Chem 3604–3615

    Google Scholar 

  78. Bhattacharya S, Thomas M (2000) DNA binding properties of novel distamycin analogs that lack the leading amide unit at the N-terminus. Biochem Biophys Res Commun 267:139–144

    Article  CAS  Google Scholar 

  79. Bhattacharya S, Thomas M (2000) Facile synthesis of oligopeptide distamycin analogs devoid of hydrogen bond donors or acceptors at the N-terminus: sequence-specific duplex DNA binding as a function of peptide chain length. Tetrahedron Lett 41:5571–5575

    Article  CAS  Google Scholar 

  80. Zaffaroni N, Lualdi S, Villa R et al (2002) Inhibition of telomerase activity by a distamycin derivative: effects on cell proliferation and induction of apoptosis in human cancer cells. Eur J Cancer 38:1792–1801

    Article  CAS  Google Scholar 

  81. Martino L, Virno A, Pagano B et al (2007) Structural and thermodynamic studies of the interaction of distamycin A with the parallel quadruplex structure [d(TGGGGT)]4. J Am Chem Soc 129:16048–16056

    Article  CAS  Google Scholar 

  82. Cosconati S, Marinelli L, Trotta R et al (2010) Structural and conformational requisites in DNA quadruplex groove binding: another piece to the puzzle. J Am Chem Soc 132:6425–6433

    Article  CAS  Google Scholar 

  83. Pagano B, Fotticchia I, De Tito S et al (2010) Selective binding of distamycin A derivative to G-quadruplex structure [d(TGGGGT)](4). J Nucleic Acids 2010: pii: 247137

    Google Scholar 

  84. Drygin D, Siddiqui-Jain A, O'Brien S et al (2009) Anticancer activity of CX-3543: a direct inhibitor of rRNA biogenesis. Cancer Res 69:7653–7661

    Article  CAS  Google Scholar 

  85. Balasubramanian S, Hurley LH, Neidle S (2011) Targeting G-quadruplexes in gene promoters: a novel anticancer strategy? Nat Rev Drug Discov 10:261–275

    Article  CAS  Google Scholar 

  86. Randazzo A, Spada GP, Webba da Silva M (2012) Circular dichroism of Quadruplex structures. Top Curr Chem DOI: 10.1007/302427_1_En_331

    Google Scholar 

  87. Petraccone L (2012) Higher-Order quadruplex structures. Top Curr Chem DOI: 10.1007/302427_1_En_350

    Google Scholar 

Download references

Acknowledgments

The authors would like to thank Dr. Jussara Amato for critical reading of the manuscript. This work was supported by the Italian “Ministero dell’Istruzione, dell’Università e della Ricerca” PRIN 2009 grant; and by the “Associazione Italiana per la Ricerca sul Cancro” [MFAG n° 11947 to B.P.]. The COST Action MP0802 is gratefully acknowledged for offering a stimulating environment for discussions on the topic.

Author information

Authors and Affiliations

  1. Dipartimento di Scienze Chimiche, Università degli Studi di Napoli “Federico II”, Via Cintia, 80126, Napoli, Italy

    Concetta Giancola

  2. Dipartimento di Chimica Farmaceutica e Tossicologica, Università degli Studi di Napoli “Federico II”, Via D. Montesano 49, 80131, Napoli, Italy

    Bruno Pagano

Authors
  1. Concetta Giancola
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bruno Pagano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Concetta Giancola or Bruno Pagano .

Editor information

Editors and Affiliations

  1. James Graham Brown Cancer Center, University of Louisville, Louisville, 40202, New York, USA

    Jonathan B. Chaires

  2. , Department of Chemistry, University of Alamaba at Birmingham, 3rd Ave 1530, Birmingham, 35294-1240, Alaska, USA

    David Graves

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Giancola, C., Pagano, B. (2012). Energetics of Ligand Binding to G-Quadruplexes. In: Chaires, J., Graves, D. (eds) Quadruplex Nucleic Acids. Topics in Current Chemistry, vol 330. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2012_347

Download citation

Publish with us

Policies and ethics

Search

Navigation