Glucose-nucleobase pairs within DNA: Impact of hydrophobicity, alternative linking unit and DNA polymerase nucleotide insertion studies

Empar Vengut-Climent, Pablo Peñalver, Ricardo Lucas, Irene Gómez-Pinto, Anna Aviñó, Alicia M. Muro-Pastor, Elsa Galbis, M. Violante De Paz, Célia Fonseca Guerra, F. Matthias Bickelhaupt, Ramón Eritja, Carlos González, Juan Carlos Morales*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


Recently, we studied glucose-nucleobase pairs, a binding motif found in aminoglycoside-RNA recognition. DNA duplexes with glucose as a nucleobase were able to hybridize and were selective for purines. They were less stable than natural DNA but still fit well on regular B-DNA. These results opened up the possible use of glucose as a non-aromatic DNA base mimic. Here, we have studied the incorporation and thermal stability of glucose with different types of anchoring units and alternative apolar sugar-nucleobase pairs. When we explored butanetriol instead of glycerol as a wider anchoring unit, we did not gain duplex thermal stability. This result confirmed the necessity of a more conformationally restricted linker to increase the overall duplex stability. Permethylated glucose-nucleobase pairs showed similar stability to glucoside-nucleobase pairs but no selectivity for a specific nucleobase, possibly due to the absence of hydrogen bonds between them. The three-dimensional structure of the duplex solved by NMR located both, the hydrophobic permethylated glucose and the nucleobase, inside the DNA helix as in the case of glucose-nucleobase pairs. Quantum chemical calculations on glucose-nucleobase pairs indicate that the attachment of the sugar to the DNA skeleton through the OH1 or OH4 positions yields the highest binding energies. Moreover, glucose was very selective for guanine when attached through OH1 or OH4 to the DNA. Finally, we examined DNA polymerase insertion of nucleotides in front of the saccharide unit. KF- polymerase from E. coli inserted A and G opposite glc and 6dglc with low efficiency but notable selectivity. It is even capable of extending the new pair although its efficiency depended on the DNA sequence. In contrast, Bst 2.0, SIII and BIOTAQ™ DNA polymerases seem to display a loop-out mechanism possibly due to the flexible glycerol linker used instead of deoxyribose.

Original languageEnglish
Pages (from-to)3544-3554
Number of pages11
JournalChemical Science
Issue number14
Early online date5 Mar 2018
Publication statusPublished - 14 Apr 2018


We thank the Ministerio de Economía y Competitividad (CTQ2011-15203-E, CTQ2012-35360, CTQ2014-52588-R, CTQ2015-64275-P, BFU2014-52864-R, and BFU2017-89707-P) and the Netherlands Organization for Scientic Research (NWO-CW and NWO-EW) for nancial support. E. V. C. thanks the Ministerio de Edu-cación, Cultura y Deporte for an FPU fellowship and Cost Action CM1005 for an STSM grant. R. L. is a recipient of a Talent Hub fellowship from Junta de Andalućıa.

FundersFunder number
Ministerio de Edu-caciónCM1005
Ministerio de Economía y CompetitividadBFU2014-52864-R, CTQ2014-52588-R, BFU2017-89707-P, CTQ2011-15203-E, CTQ2015-64275-P, CTQ2012-35360
Junta de Andalucía


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