Anomeric DNA: Functionalization of α-d Anomers of 7-Deaza-2′-deoxyadenosine and 2′-Deoxyuridine with Clickable Side Chains and Click Adducts in Homochiral and Heterochiral Double Helices

Abstract

Anomeric base pairs in heterochiral DNA with strands in the α-d and β-d configurations and homochiral DNA with both strands in α-d configuration were functionalized. The α-d anomers of 2′-deoxyuridine and 7-deaza-2′-deoxyadenosine were synthesized and functionalized with clickable octadiynyl side chains. Nucleosides were protected and converted to phosphoramidites. Solid-phase synthesis furnished 12-mer oligonucleotides, which were hybridized. Pyrene click adducts display fluorescence, a few of them with excimer emission. Tm values and thermodynamic data revealed the following order of duplex stability α/α-d≫β/β-d≥α/β-d. CD spectra disclosed that conformational changes occur during hybridization. Functionalized DNAs were modeled and energy minimized. Clickable side chains and bulky click adducts are well accommodated in the grooves of anomeric DNA. The investigation shows for the first time that anomeric DNAs can be functionalized in the same way as canonical DNA for potential applications in nucleic acid chemistry, chemical biology, and DNA material science.