Bipyridyl‐ and Biphenyl‐DNA: A Recognition Motif Based on Interstrand Aromatic Stacking

Abstract

The synthesis and incorporation into oligonucleotides of C-nucleosides containing the two aromatic, non-hydrogen-bonding nucleobase substitutes biphenyl (I) and bipyridyl (Y) are described. Their homo- and hetero-recognition properties in different sequential arrangements were then investigated via UV-melting curve analysis, gel mobility assays, CD- and NMR spectroscopy. An NMR analysis of a dodecamer duplex containing one biphenyl pair in the center, as well as CD data on duplexes with multiple insertions provide further evidence for the zipper-like interstrand stacking motif that we proposed earlier based on molecular modeling. UV-thermal melting experiments with duplexes containing one to up to seven I- or Y base pairs revealed a constant increase in T(m) in the case of I and a constant decrease for Y. Mixed I/Y base pairs lead to stabilities in between the homoseries. Insertion of alternating I/abasic site- or Y/abasic site pairs strongly decreases the thermal stability of duplexes. Asymmetric distribution of I- or Y residues on either strand of the duplex were also investigated in this context. Duplexes with three natural base pairs at both ends and 50 % of I pairs in the center are still readily formed, while duplexes with blunt ended I pairs tend to aggregate unspecifically. Duplexes with one natural overhang at the end of a I-I base pair tract can both aggregate or form ordered duplexes, depending on the nature of the natural bases in the overhang.

2‐Phenanthrenyl–DNA: Synthesis, Pairing, and Fluorescence Properties

“…[26][27][28] A recent NMR structure confirmed the interstrand stacking motif for a system with one biphenyl pair. [29] In addition we could show that the remote biphenyl rings can be equipped with acceptor or donor substituents without alteration of the overall duplex architecture.…”

A New Modular and Practical Methodology for the Synthesis of 4‐ or 3‐Substituted Phenyl C‐Nucleosides

“…Thus the 4-bromophenyl nucleoside 2 was subjected to a series of Pd-catalyzed crosscouplings with 4-fluorophenyl-and 2-naphthylboronic acids (Scheme 2, Table 2, Entries 1,2), 2-(tributylstannyl)thiophene (Entry 3), triethylaluminium (Entry 4) and benzylzinc chloride (Entry 5). All these reactions were performed under standard conditions for each type of reaction without any optimization using standard catalysis of Pd(PPh 3 ) 4 . In all cases the desired 4-substituted phenyl nucleosides 6a-6e were obtained in good isolated yields of ca.…”

“…The mixture was stirred at room temp. for 12 h, poured onto ice containing NH 4 Cl, exctracted to ethyl acetate (2 × 100 mL), evaporated, and chromatographed on a silica gel column (hexanes/EA, 10:1) to get products 2 and 3 or 4 and 5. www.eurjoc.org 4527 omer 3 or 5 (1 mmol) in dichloromethane (50 mL) (in case of 5, 1 mL of H 2 SO 4 was also added). The mixture was stirred at 40°C for 24 h and then poured onto ice containing NaHCO 3 .…”

“…[5] There is a number of synthetic approaches to C-nucleosides. [6] The most general methodologies are (i) additions of organometallics to ribono-or 2-deoxyribonolactones [4,7] or (ii) coupling of a halogenose with organometallics. [8,9] The latter approach using diaryl cadmium reagents [5,8] is the most commonly used method for aryl and biaryl C-nucleosides.…”

“…[4] Biaryl or even oligoaryl C-nucleosides have also been used as fluorophoric probes. [5] There is a number of synthetic approaches to C-nucleosides.…”