Carbohydrate-DNA Interactions at G-Quadruplexes: Folding and Stability Changes by Attaching Sugars at the 5′-End

• Published in: Chemistry : a European journal Vol. 19; no. 6; pp. 1920 - 1927
• Main Authors: Gómez-Pinto, Irene, Vengut-Climent, Empar, Lucas, Ricardo, Aviñó, Anna, Eritja, Ramón, González, Carlos, Morales, Juan Carlos
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 04.02.2013; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Aptamers, Nucleotide - chemistry; Aptamers, Nucleotide - metabolism; Carbohydrates; Carbohydrates - chemistry; Chemistry; Conjugates; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA - metabolism; Folding; G-Quadruplexes; Humans; Hydrogen Bonding; hydrogen bonds; Joining; Ligands; Magnetic Resonance Spectroscopy; molecular interactions; Molecular Structure; Solutions; Stacking; Sugars; Telomere - chemistry; Telomere - metabolism
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201203902

Quadruplex DNA structures are attracting an enormous interest in many areas of chemistry, ranging from chemical biology, supramolecular chemistry to nanoscience. We have prepared carbohydrate–DNA conjugates containing the oligonucleotide sequences of G‐quadruplexes (thrombin binding aptamer (TBA) and human telomere (TEL)), measured their thermal stability and studied their structure in solution by using NMR and molecular dynamics. The solution structure of a fucose–TBA conjugate shows stacking interactions between the carbohydrate and the DNA G‐tetrad in addition to hydrogen bonding and hydrophobic contacts. We have also shown that attaching carbohydrates at the 5′‐end of a quadruplex telomeric sequence can alter its folding topology. These results suggest the possibility of modulating the folding of the G‐quadruplex by linking carbohydrates and have clear implications in molecular recognition and the design of new G‐quadruplex ligands. Sweetening G‐quadruplexes: Carbohydrate–DNA contacts are observed in a G‐quadruplex context. Mono‐ and disaccharides attached to the 5′ end of the thrombin‐binding aptamer (TBA) are capable of stabilizing the conjugate with respect to the spacer‐TBA control. A detailed structure elucidation of the fucose–TBA conjugate shows sugar stacking on the guanine tetrad together with methyl–methyl van der Waals interactions and a possible hydrogen bond (see figure).