| Abstract
| - Sugar−oligoamides have been designed and synthesized as structurally simple carbohydrate-based ligands to study carbohydrate−DNA interactions. The general design of the ligands 1−3 has beendone as to favor the bound conformation of Distamycin-type γ-linked covalent dimers which is a hairpinconformation. Indeed, NMR analysis of the sugar−oligoamides in the free state has indicated the presenceof a percentage of a hairpin conformation in aqueous solution. The DNA binding activity of compounds1−3 was confirmed by calf thymus DNA (ct-DNA) NMR titration. Interestingly, the binding of the differentsugar−oligoamides seems to be modulated by the sugar configuration. Semiquantitative structuralinformation about the DNA ligand complexes has been derived from NMR data. A competition experimentwith Netropsin suggested that the sugar−oligoamide 3 bind to DNA in the minor groove. The NMR titrationsof 1-3 with poly(dA-dT) and poly(dG-dC) suggested preferential binding to the ATAT sequence. TR-NOENMR experiments for the sugar−oligoamide 3−ct-DNA complex both in D2O and H2O have confirmed thecomplex formation and given information on the conformation of the ligand in the bound state. The dataconfirmed that the sugar−oligoamide ligand is a hairpin in the bound state. Even more relevant to ourgoal, structural information on the conformation around the N-glycosidic linkage has been accessed. Thus,the sugar asymmetric centers pointing to the NH-amide and N-methyl rims of the molecule have beencharacterized.
|
