A Neutral DNA Sequence‐Selective Vector for Interaction Studies: Fluorescence Binding Experiments Directed Towards a Carbohydrate‐DNA Carrier

The distamycin‐type γ‐linked covalent dimer ‐Py‐γ‐Py‐Ind has been shown to be a neutral selective vector capable of transporting recognition elements to the minor groove of DNA for further structural studies. Comparison of fluorescence binding constants of the complexes formed by the vectors (R‐Py‐γ‐Py‐Ind 1 and 3 ) with ct ‐DNA and poly (dA‐dT) showed that ‐Py‐γ‐Py‐Ind is a neutral (–ATAT–)‐selective vector. We also provide experimental data that show that the vector can be used as a sugar‐carrier to the DNA. Thus, modifying the vector at the C terminus with sugars of different configurations ( 4 – 7 D vs. 8 L ), and with both α‐ and β‐linkages ( 5 and 4 , respectively) to the oligoamide fragment provides efficient DNA binders ( K a = 1.1 × 10 4 to 3.2 × 10 5 M –1 ). Moreover, the sugar residue is able to modulate the binding to the different DNA polymers studied and, even more relevantly, the sugar contributes to the selectivity of binding: β‐ D ‐Gal‐Py‐γ‐Py‐Ind ( 6 ) is the most selective –ATAT–sugar–oligoamide ligand {ΔΔ G° 6 [ poly (dA‐dT) – ct ‐DNA] = –4.0 kcal mol –1 }. We have used fluorescence quantum yield values to ensure the presence of similar free state conformation for ligands 1 – 8 and we can thus correlate the differences in the measured binding energies with the changes in the shape of the structural elements. Finally, we have demonstrated that the sequence‐selective sugar carrier makes a 1:1 complex with the Drew–Dickerson oligonucleotide dodecamer, thus opening the road to more detailed structural and thermodynamic studies of sugar‐oligoamide DNA short oligonucleotide complexes in solution. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)