Advertisement

Analytical and Bioanalytical Chemistry

, Volume 411, Issue 20, pp 5197–5207 | Cite as

Effect of structure levels on surface-enhanced Raman scattering of human telomeric G-quadruplexes in diluted and crowded media

  • Francesco PapiEmail author
  • Adriana Kenđel
  • Marina Ratkaj
  • Ivo Piantanida
  • Paola Gratteri
  • Carla Bazzicalupi
  • Snežana MiljanićEmail author
Research Paper

Abstract

Human telomeric G-quadruplexes are emerging targets in anticancer drug discovery since they are able to efficiently inhibit telomerase, an enzyme which is greatly involved in telomere instability and immortalization process in malignant cells. G-quadruplex (G4) DNA is highly polymorphic and can adopt different topologies upon addition of electrolytes, additives, and ligands. The study of G-quadruplex forms under various conditions, however, might be quite challenging. In this work, surface-enhanced Raman scattering (SERS) spectroscopy has been applied to study G-quadruplexes formed by human telomeric sequences, d[A3G3(TTAGGG)3A2] (Tel26) and d[(TTAGGG)4T2] (wtTel26), under dilute and crowding conditions. The SERS spectra distinctive of hybrid-1 and hybrid-2 G-quadruplexes of Tel26 and wtTel26, respectively, were observed for the sequences folded in the presence of K+ ions (110 mM) in a buffered solution, representing the diluted medium. Polyethylene glycol (5, 10, 15, 20, and 40% v/v PEG) was used to create a molecular-crowded environment, resulting in the formation of the parallel G-quadruplexes of both studied human telomeric sequences. Despite extensive overlap by the crowding agent bands, the SERS spectral features indicative of parallel G4 form of Tel26 were recognized. The obtained results implied that SERS of G-quadruplexes reflected not only the primary structure of the studied human telomeric sequence, including its nucleobase composition and sequence, but also its secondary structure in the sense of Hoogsteen hydrogen bonds responsible for the guanine tetrad formation, and finally its tertiary structure, defining a three-dimensional DNA shape, positioned close to the enhancing metallic surface.

Graphical abstract

Keywords

Structure level SERS CD G-quadruplex Human telomere Crowding 

Notes

Acknowledgments

We thank Ente Cassa Risparmio Firenze for a grant to FP (ECR2014.0309) and the University of Florence for funding FP’s stay in Zagreb (Contributo di Ateneo per la Promozione delle Attività Internazionali Anno 2015 and Piano di Internazionalizzazione di Ateneo 2013-2015).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

216_2019_1894_MOESM1_ESM.pdf (200 kb)
ESM 1 (PDF 199 kb)

References

  1. 1.
    Murat P, Balasubramanian S. Existence and consequences of G-quadruplex structures in DNA. Curr Opin Genet Dev. 2014;25:22–9.CrossRefGoogle Scholar
  2. 2.
    Maizels N, Gray LT. The G4 genome. PLoS Genet. 2013;9:e1003468.CrossRefGoogle Scholar
  3. 3.
    Burge S, Parkinson GN, Hazel P, Todd AK, Neidle S. Quadruplex DNA: sequence, topology and structure. Nucleic Acids Res. 2006;34:5402–15.CrossRefGoogle Scholar
  4. 4.
    Zaccaria F, Paragi G, Guerra CF. The role of alkali metal cations in the stabilization of guanine quadruplexes: why K+ is the best. Phys Chem Chem Phys. 2016;18:20895–04.CrossRefGoogle Scholar
  5. 5.
    Bhattacharyya D, Arachchilage GM, Basu S. Metal cations in G-quadruplex folding and stability. Front Chem. 2016;4:38.CrossRefGoogle Scholar
  6. 6.
    Lam EYN, Beraldi D, Tannahill D, Balasubramanian S. G-quadruplex structures are stable and detectable in human genomic DNA. Nat Commun. 2013;4:1796.CrossRefGoogle Scholar
  7. 7.
    Biffi G, Tannahill D, McCafferty J, Balasubramanian S. Quantitative visualization of DNA G-quadruplex structures in human cells. Nat Chem. 2013;5:182–6.CrossRefGoogle Scholar
  8. 8.
    Biffi G, Tannahill D, Miller J, Howat WJ, Balasubramanian S. Elevated levels of G-quadruplex formation in human stomach and liver cancer tissues. PLoS One. 2014;9:e102711.CrossRefGoogle Scholar
  9. 9.
    Chambers VS, Marsico G, Boutell JM, Di Antonio M, Smith GP, Balasubramanian S. High-throughput sequencing of DNA G-quadruplex structures in the human genome. Nat Biotechnol. 2015;33:877–81.CrossRefGoogle Scholar
  10. 10.
    Hänsel-Hertsch R, Beraldi D, Lensing SV, Marsico G, Zyner K, Parry A, et al. G-quadruplex structures mark human regulatory chromatin. Nat Genet. 2016;48:1267–72.CrossRefGoogle Scholar
  11. 11.
    Rhodes D, Lipps HJ. G-quadruplexes and their regulatory roles in biology. Nucleic Acids Res. 2015;43:8627–37.CrossRefGoogle Scholar
  12. 12.
    Balasubramanian S, Neidle S. G-quadruplex nucleic acids as therapeutic targets. Curr Opin Chem Biol. 2009;13:345–53.CrossRefGoogle Scholar
  13. 13.
    Maji B, Bhattacharya S. Advances in the molecular design of potential anticancer agents via targeting of human telomeric DNA. Chem Commun. 2014;50:6422–38.CrossRefGoogle Scholar
  14. 14.
    Ohnmacht SA, Neidle S. Small-molecule quadruplex-targeted drug discovery. Bioorganic Med Chem Lett. 2014;24:2602–12.CrossRefGoogle Scholar
  15. 15.
    Neidle S. Quadruplex nucleic acids as novel therapeutic targets. J Med Chem. 2016;59:5987–11.CrossRefGoogle Scholar
  16. 16.
    Li J, Correia JJ, Wang L, Trent JO, Chaires JB. Not so crystal clear: the structure of the human telomere G-quadruplex in solution differs from that present in a crystal. Nucleic Acids Res. 2005;33:4649–59.CrossRefGoogle Scholar
  17. 17.
    Dai J, Carver M, Yang D. Polymorphism of human telomeric quadruplex structures. Biochimie. 2008;90:1172–83.CrossRefGoogle Scholar
  18. 18.
    Phan AT. Human telomeric G-quadruplex: structures of DNA and RNA sequences. FEBS J. 2010;277:1107–17.CrossRefGoogle Scholar
  19. 19.
    Parkinson GN, Lee MP, Neidle S. Crystal structure of parallel quadruplexes from human telomeric DNA. Nature. 2002;417:876–80.CrossRefGoogle Scholar
  20. 20.
    Ambrus A, Chen D, Dai J, Bialis T, Jones RA, Yang D. Human telomeric sequence forms a hybrid-type intramolecular G-quadruplex structure with mixed parallel/antiparallel strands in potassium solution. Nucleic Acids Res. 2006;34:2723–35.CrossRefGoogle Scholar
  21. 21.
    Renčiuk D, Kejnovská I, Školáková P, Bednářová K, Motlová J, Vorlíčková M. Arrangements of human telomere DNA quadruplex in physiologically relevant K+ solutions. Nucleic Acids Res. 2009;37:6625–34.CrossRefGoogle Scholar
  22. 22.
    Hänsel-Hertsch R, Löhr F, Foldynová-Trantírková S, Bamberg E, Trantírek L, Dötsch V. The parallel G-quadruplex structure of vertebrate telomeric repeat sequences is not the preferred folding topology under physiological conditions. Nucleic Acids Res. 2011;39:5768–75.CrossRefGoogle Scholar
  23. 23.
    Lane AN, Chaires JB, Gray RD, Trent JO. Stability and kinetics of G-quadruplex structures. Nucleic Acids Res. 2008;36:5482–15.CrossRefGoogle Scholar
  24. 24.
    Bugaut A, Balasubramanian S. A sequence-independent study of the influence of short loop lengths on the stability and topology of intramolecular DNA G-quadruplexes. Biochem. 2008;47:689–97.CrossRefGoogle Scholar
  25. 25.
    Martino L, Pagano B, Fotticchia I, Neidle S, Giancola C. Shedding light on the interaction between TMPyP4 and human telomeric quadruplexes. J Phys Chem B. 2009;113:14779–86.CrossRefGoogle Scholar
  26. 26.
    Petraccone L, Pagano B, Giancola C. Studying the effect of crowding and dehydration on DNA G-quadruplexes. Methods. 2012;57:76–83.CrossRefGoogle Scholar
  27. 27.
    Tippana R, Xiao W, Myong S. G-quadruplex conformation and dynamics are determined by loop length and sequence. Nucleic Acids Res. 2014;42:8106–14.CrossRefGoogle Scholar
  28. 28.
    Miyoshi D, Karimata H, Sugimoto N. Hydration regulates thermodynamics of G-quadruplex formation under molecular crowding conditions. J Am Chem Soc. 2006;128:7957–63.CrossRefGoogle Scholar
  29. 29.
    Xu L, Feng S, Zhou X. Human telomeric G-quadruplexes undergo dynamic conversion in a molecular crowding environment. Chem Commun. 2011;47:3517–9.CrossRefGoogle Scholar
  30. 30.
    Dai J, Punchihewa C, Ambrus A, Chen D, Jones RA, Yang D. Structure of the intramolecular human telomeric G-quadruplex in potassium solution: a novel adenine triple formation. Nucleic Acids Res. 2007;35:2440–50 (PDB ID: 2HY9).CrossRefGoogle Scholar
  31. 31.
    Dai J, Carver M, Punchihewa C, Jones RA, Yang D. 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. 2007;35:4927–40 (PDB ID: 2JPZ).CrossRefGoogle Scholar
  32. 32.
    Xue Y, Z-y K, Wang Q, Yao Y, Liu J, Hao Y-h, et al. Human telomeric DNA forms parallel-stranded intramolecular G-quadruplex in K+ solution under molecular crowding condition. J Am Chem Soc. 2007;129:11185–91.CrossRefGoogle Scholar
  33. 33.
    Heddi B, Phan AT. Structure of human telomeric DNA in crowded solution. J Am Chem Soc. 2011;133:9824–33.CrossRefGoogle Scholar
  34. 34.
    Lim KW, Amrane S, Bouaziz S, Xu W, Mu Y, Patel DJ, et al. Structure of the human telomere in K+ solution: a stable basket-type G-quadruplex with only two G-tetrad layers. J Am Chem Soc. 2009;131:4301–9.CrossRefGoogle Scholar
  35. 35.
    Zhang Z, Dai J, Veliath E, Jones RA, Yang D. Structure of a two-G-tetrad intramolecular G-quadruplex formed by a variant human telomeric sequence in K+ solution: insights into the interconversion of human telomeric G-quadruplex structures. Nucleic Acids Res. 2009;38:1009–21.CrossRefGoogle Scholar
  36. 36.
    Luu KN, Phan AT, Kuryavyi V, Lacroix L, Patel DJ. Structure of the human telomere in K+ solution: an intramolecular (3+1) G-quadruplex scaffold. J Am Chem Soc. 2006;128:9963–70.CrossRefGoogle Scholar
  37. 37.
    Phan AT, Kuryavyi V, Luu KN, Patel DJ. Structure of two intramolecular G-quadruplexes formed by natural human telomere sequences in K+ solution. Nucleic Acids Res. 2007;35:6517–25.CrossRefGoogle Scholar
  38. 38.
    Hänsel-Hertsch R, Löhr F, Trantírek L, Dötsch V. High-resolution insight into G-overhang architecture. J Am Chem Soc. 2013;135:2816–24.CrossRefGoogle Scholar
  39. 39.
    Buscaglia R, Miller MC, Dean WL, Gray RD, Lane AN, Trent JO, et al. Polyethylene glycol binding alters human telomere G-quadruplex structure by conformational selection. Nucleic Acids Res. 2013;41:7934–46.CrossRefGoogle Scholar
  40. 40.
    Neidle S. The structures of quadruplex nucleic acids and their drug complexes. Curr Opin Struct Biol. 2009;19:239–50.CrossRefGoogle Scholar
  41. 41.
    Alvarez-Puebla RA, Liz-Marzán LM. SERS-based diagnosis and biodetection. Small. 2010;6:604–10.CrossRefGoogle Scholar
  42. 42.
    Bantz KC, Meyer AF, Wittenberg NJ, Im H, Kurtuluş Ö, Lee SH, et al. Recent progress in SERS biosensing. Phys Chem Chem Phys. 2011;13:11551–67.CrossRefGoogle Scholar
  43. 43.
    Xie W, Schlücker S. Medical applications of surface-enhanced Raman scattering. Phys Chem Chem Phys. 2013;15:5329–44.CrossRefGoogle Scholar
  44. 44.
    Cialla D, Pollok S, Steinbrücker C, Weber K, Popp J. SERS-based detection of biomolecules. Nanophotonics. 2014;3:383–11.CrossRefGoogle Scholar
  45. 45.
    Joseph MM, Narayanan N, Nair JB, Karunakaran V, Ramya AN, Sujai PT, et al. Exploring the margins of SERS in practical domain: an emerging diagnostic modality for modern biomedical applications. Biomaterials. 2018;181:140–81.CrossRefGoogle Scholar
  46. 46.
    Zheng X-S, Jahn IJ, Weber K, Cialla D, Popp J. Label-free SERS in biological and biomedical applications: recent progress, current challenges and opportunities. Spectrochim Acta A. 2018;197:56–77.CrossRefGoogle Scholar
  47. 47.
    Miljanić S, Ratkaj M, Matković M, Piantanida I, Gratteri P, Bazzicalupi C. Assessment of human telomeric G-quadruplex structures using surface-enhanced Raman spectroscopy. Anal Bioanal Chem. 2017;409:2285–95.CrossRefGoogle Scholar
  48. 48.
    Petraccone L, Malafronte A, Amato J, Giancola C. G-quadruplexes from human telomeric DNA: how many conformations in PEG containing solutions? J Phys Chem B. 2012;116:2294–305.CrossRefGoogle Scholar
  49. 49.
    Munro C, Smith W, Garner M, Clarkson J, White P. Characterization of the surface of a citrate-reduced colloid optimized for use as a substrate for surface-enhanced resonance Raman scattering. Langmuir. 1995;11:3712–20.CrossRefGoogle Scholar
  50. 50.
    Torres-Nunez A, Faulds K, Graham D, Alvarez-Puebla RA, Guerrini L. Silver colloids as plasmonic substrate for direct label-free surface-enhanced Raman scattering analysis of DNA. Analyst. 2016;141:5170–80.CrossRefGoogle Scholar
  51. 51.
    Dick S, Bell SE. Quantitative surface-enhanced Raman spectroscopy of single bases in oligonucleotides. Faraday Discuss. 2017;205:517–36.CrossRefGoogle Scholar
  52. 52.
    Guerrini L, Krpetić Ž, van Lierop D, Alvarez-Puebla RA, Graham D. Direct surface-enhanced Raman scattering analysis of DNA duplexes. Angew Chem Int Ed. 2015;54:1144–8.CrossRefGoogle Scholar
  53. 53.
    Garcia-Rico E, Alavarez-Puebla RA, Guerrini L. Direct surface-enhanced Raman scattering (SERS) spectroscopy of nucleic acids: from fundamental to real-life applications. Chem Soc Rev. 2018;47:4909–23.CrossRefGoogle Scholar
  54. 54.
    Pagba CV, Lane SM, Wachsmann-Hogiu S. Raman and surface-enhanced Raman spectroscopic studies of the 15-mer DNA thrombin-binding aptamer. J Raman Spectrosc. 2010;41:241–7.Google Scholar
  55. 55.
    Rusciano G, De Luca AC, Pesce G, Sasso A, Oliviero G, Amato J, et al. Label-free probing of G-quadruplex formation by surface-enhanced Raman scattering. Anal Chem. 2011;83:6849–55.CrossRefGoogle Scholar
  56. 56.
    Li Y, Han X, Zhou S, Yan Y, Xiang X, Zhao B, et al. Structural features of DNA G-quadruplexes revealed by surface-enhanced Raman spectroscopy. J Phys Chem Lett. 2018;9:3245–52.CrossRefGoogle Scholar
  57. 57.
    Nakamoto K, Tsuboi M, Strahan GD. Drug-DNA interactions: structures and spectra. Hoboken: Wiley; 2008.CrossRefGoogle Scholar
  58. 58.
    Krafft C, Benevides JM, Thomas GJ. Secondary structure polymorphism in Oxytricha nova telomeric DNA. Nucleic Acids Res. 2002;30:3981–91.CrossRefGoogle Scholar
  59. 59.
    Benevides JM, Overman SA, Thomas GJ. Raman, polarized Raman and ultraviolet resonance Raman spectroscopy of nucleic acids and their complexes. J Raman Spectrosc. 2005;36:279–99.CrossRefGoogle Scholar
  60. 60.
    Pagba CV, Lane SM, Wachsmann-Hogiu S. Conformational changes in quadruplex oligonucleotide structures probed by Raman spectroscopy. Biomed Opt Express. 2011;2:207–17.CrossRefGoogle Scholar
  61. 61.
    Palacký J, Vorlíčková M, Kejnovská I, Mojzeš P. Polymorphism of human telomeric quadruplex structure controlled by DNA concentration: a Raman study. Nucleic Acids Res. 2012;41:1005–16.CrossRefGoogle Scholar
  62. 62.
    Friedman SJ, Terentis AC. Analysis of G-quadruplex conformations using Raman and polarized Raman spectroscopy. J Raman Spectrosc. 2016;47:259–68.CrossRefGoogle Scholar
  63. 63.
    Aroca R. Surface-enhanced vibrational spectroscopy. Chichester: Wiley; 2006.CrossRefGoogle Scholar
  64. 64.
    Schlücker S. Surface-enhanced Raman spectroscopy: analytical, biophysical and life science applications. Weinheim: Wiley-VCH; 2011.Google Scholar
  65. 65.
    Schlücker S. Surface-enhanced Raman spectroscopy: concepts and chemical applications. Angew Chem Int Ed. 2014;53:4756–95.CrossRefGoogle Scholar
  66. 66.
    Papadopoulou E, Bell SE. Structure of adenine on metal nanoparticles: pH equilibria and formation of Ag+ complexes detected by surface-enhanced Raman spectroscopy. J Phys Chem C. 2010;114:22644–51.CrossRefGoogle Scholar
  67. 67.
    Pagliai M, Caporali S, Muniz-Miranda M, Pratesi G, Schettino V. SERS, XPS, and DFT study of adenine adsorption on silver and gold surfaces. J Phys Chem Lett. 2012;3:242–5.CrossRefGoogle Scholar
  68. 68.
    Miljanić S, Dijanošić A, Matić I. Adsorption mechanisms of RNA mononucleotides on silver nanoparticles. Spectrochim Acta A. 2015;137:1357–62.CrossRefGoogle Scholar
  69. 69.
    Barhoumi A, Zhang D, Tam F, Halas NJ. Surface-enhanced Raman spectroscopy of DNA. J Am Chem Soc. 2008;130:5523–9.CrossRefGoogle Scholar
  70. 70.
    Karakoti AS, Das S, Thevuthasan S, Seal S. PEGylated inorganic nanoparticles. Angew Chem Int Ed. 2011;50:1980–94.CrossRefGoogle Scholar
  71. 71.
    Chang W-C, Tai J-T, Wang H-F, Ho R-M, Hsiao T-C, Tsai D-H. Surface PEGylation of silver nanoparticles: kinetics of simultaneous surface dissolution and molecular desorption. Langmuir. 2016;32:9807–15.CrossRefGoogle Scholar
  72. 72.
    Paramasivan S, Rujan I, Bolton PH. Circular dichroism of quadruplex DNAs: applications to structure, cation effects and ligand binding. Methods. 2007;43:324–31.CrossRefGoogle Scholar
  73. 73.
    Vorlíčková M, Kejnovská I, Sagi J, Renčiuk D, Bednářová K, Motlová J, et al. Circular dichroism and guanine quadruplexes. Methods. 2012;57:64–75.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Chemistry “Ugo Schiff”University of FlorenceFlorenceItaly
  2. 2.Department NEUROFARBA – Pharmaceutical and Nutraceutical Section, Laboratory of Molecular Modeling Cheminformatics & QSARUniversity of FlorenceFlorenceItaly
  3. 3.Division of Analytical Chemistry, Department of Chemistry, Faculty of ScienceUniversity of ZagrebZagrebCroatia
  4. 4.Teva Pharmaceutical Industries Ltd., Research and DevelopmentPLIVA CroatiaZagrebCroatia
  5. 5.Division of Organic Chemistry and BiochemistryRuđer Bošković InstituteZagrebCroatia

Personalised recommendations