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.

Purine–Purine Base Pairs in Parallel DNA: β-D Anomeric 8-Aza-7-deazaisoguanine and 7-Functionalized Conjugates Form Stable Base Pairs with α-D 5-Aza-7-deaza-2′-deoxyguanosine

“…However, various factors contribute to shape differences of CD spectra: (i) the conformation of the monomers which can be syn or anti , (ii) the conformation of the sugar residues ( N vs S ), (iii) the hydrogen-bonding network formed between nucleobases, (iv) stacking interactions between nucleobases or base pairs, and (v) the helicity of the duplex (+ or −). Previous CD experiments have shown that CD spectra of α-D anomeric single strands display spectra with mirror-like Cotton effects with respect to the β-strand. , Herein, we focus on the helix structures of the purine–purine tracts in anomeric DNA and the positional impact of side chains. Our DNA fragments represent a full helix turn that contains all four DNA bases in random composition with and without clickable side chains.…”

“…Previous CD experiments have shown that CD spectra of α-D anomeric single strands display spectra with mirror-like Cotton effects with respect to the βstrand. 24,37 Herein, we focus on the helix structures of the purine−purine tracts in anomeric DNA and the positional impact of side chains. Our DNA fragments represent a full helix turn that contains all four DNA bases in random composition with and without clickable side chains.…”

“…Herein, we investigate purine base pairing in heterochiral DNA with strands in parallel orientation. Previously, parallel Watson–Crick DNA was constructed on the basis of heterochiral DNA, − or it has been realized with so-called isonucleosides. − This DNA was constructed utilizing isoguanine–cytosine and isocytosine–guanine base pairs in which amino groups and oxo groups of canonical nucleosides switched their position. This changed the donor–acceptor pattern in base pairs including strand orientation.…”

Purine DNA Constructs Designed to Expand the Genetic Code: Functionalization, Impact of Ionic Forms, and Molecular Recognition of 7-Deazaxanthine–7-Deazapurine-2,6-diamine Base Pairs and Their Purine Counterparts

“…1 H NMR (DMSO-d 6 , 300 MHz): δ 11.63 (s, 1H, NH), 10.67 (s, 1H, NH), 7.09 (s, 1H, H-8), 6.86 (m, 1H, C�CH), 6.86 (dd, 1H, H-1′), 5.58 (s, 1H, OH-5′), 5.28 (d, J = 3.6 Hz, 1H, OH-3′), 4.30 (dq, J = 5.9, 2.9 Hz, 1H, H-3′), 3.84 (q, J = 3. 3 [2,3-d]pyrimidin-2-one (10). Compound 6 (0.40 g, 0.98 mmol) was dissolved in dry DMF (8 mL) and degassed for 5 min with argon.…”

“…The residue was purified by FC (silica gel, column 8 × 3 cm, CH 2 Cl 2 /MeOH, 98:2 to 95:5), affording compound 17 (400 mg, 82%) as light blue solid. TLC (CH 2 Cl 2 / MeOH, 95:5) R f 0.2. λ max (MeOH)/nm 243 (ε/dm 3 mol −1 cm −1 13 600), 277 (10,700). 1 H NMR (DMSO-d 6 , 600 MHz): δ 6.95 (d, J = 3.6 Hz, 1H, H-8), 6.34 (d, J = 3.6 Hz, 1H, H-7), 6.16 (dd, J = 8.0, 6.0 Hz, 1H, H-1′), 5.79 (d, J = 1.3 Hz, 2H, CH 2 ), 5.28 (d, J = 3.7 Hz, 1H, OH-3′), 4.29 (dt, J = 6.0, 2.9 Hz, 1H, H-3′), 3.83 (q, J = 3.2 Hz, 1H, H-4′), 3.56 (t, J = 3.1 Hz, 2H, 2× H-5′), 2.27 (ddd, J = 13.6, 8.0, 5.8 Hz, 1H, H-2 β ′), 2.15 (ddd, J = 13.2, 5.9, 2.6 Hz, 1H, H-2 α ′), and 1.07 (s, 9H, CH 3 ).…”