2024-03-29T05:06:52Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1157852020-10-07T12:33:10Zcom_10261_33com_10261_5com_10261_86com_10261_1col_10261_286col_10261_339
2015-05-27T09:49:19Z
urn:hdl:10261/115785
Cooperative hydrogen bonding in glyco-oligoamides: DNA minor groove binders in aqueous media
Blázquez-Sánchez, M. Teresa
Marcelo, Filipa
Fernández-Alonso, M. Carmen
Poveda, Ana
Jiménez-Barbero, Jesús
Vicent, Cristina
Cooperativity
Hydrogen bonds
Pi interactions
Carbohydrates
DNA
A strategy to create cooperative hydrogen-bonding centers by using strong and directional intramolecular hydrogen-bonding motifs that can survive in aqueous media is presented. In particular, glyco-oligoamides, a family of DNA minor groove binders, with cooperative and non-cooperative hydrogen-bonding donor centers in the carbohydrate residues have been designed, synthesized, and studied by means of NMR spectroscopy and molecular modeling methods. Indeed, two different sugar moieties, namely, β-D-Man-Py-γ-Py-Ind (1; Ind = indole, Man = mannose, Py= pyrrole) and β-D-Tal-Py-γ-Py-Ind (2; Tal = talose), were chosen according to our design. These sugar molecules should present oneor two-directional intramolecular hydrogen bonds. The challenge has been to study the conformation of the glyco-oligoamides at low temperature in physiological media by detecting the exchangeable protons (amide NH and OH resonances) by means of NMR spectroscopic analysis. In addition, two more glyco-oligoamides with non-cooperative hydrogen-bonding centers, that is, β-D-Glc-Py-γ-Py-Ind (3; Glc = glucose), β-D-Gal-Py-γ-Py-Ind (4; Gal = galac-tose), and the model compounds β-D-Man-Py-NHAc (5) and β-D-Tal-Py-NHAc (6) were synthesized and studied for comparison. We have demonstrated the existence of directional intramolecular hydrogen bonds in 1 and 2 in aqueous media. The unexpected differences in terms of stabilization of the intramolecular hydrogen bonds in 1 and 2 relative to 5 and 6 promoted us to evaluate the influence of CH-π interactions on the establishment of intramolecular hydrogen bonds by using computational methods. Initial binding studies of 1 and 2 with calf-thymus DNA and poly(dA-dT)2 by NMR spectroscopic analysis and molecular dynamics simulations were also carried out. Both new sugar-oligoamides are bound in the minor groove of DNA, thus keeping a stable hairpin structure, as in the free state, in which both intramolecular hydrogen-bonding and CH-π interactions are present.
2015-05-27T09:49:19Z
2015-05-27T09:49:19Z
2014
2015-05-27T09:49:19Z
artículo
Chemistry - A European Journal 20: 17640-17652 (2014)
http://hdl.handle.net/10261/115785
10.1002/chem.201403911
eng
closedAccess
John Wiley & Sons