Back to Search
Start Over
Cooperative hydrogen bonding in glyco-oligoamides: DNA minor groove binders in aqueous media
- Source :
- Digital.CSIC. Repositorio Institucional del CSIC, instname
- Publication Year :
- 2014
- Publisher :
- John Wiley & Sons, 2014.
-
Abstract
- 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.
- Subjects :
- Models, Molecular
Magnetic Resonance Spectroscopy
Cooperativity
Carbohydrates
Catalysis
Hydrogen bonds
chemistry.chemical_compound
Molecular recognition
Amide
Pi interactions
Animals
Organic chemistry
Molecule
Binding Sites
Molecular Structure
Hydrogen bond
Chemistry
Organic Chemistry
Temperature
Water
Hydrogen Bonding
Talose
General Chemistry
Nuclear magnetic resonance spectroscopy
DNA
Amides
Crystallography
Intramolecular force
Nucleic Acid Conformation
Cattle
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Digital.CSIC. Repositorio Institucional del CSIC, instname
- Accession number :
- edsair.doi.dedup.....29352237ea7663e619a23c85be2f55e4