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


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


Structure level SERS CD G-quadruplex Human telomere Crowding 



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)


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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

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