Oligonucleotides Containing 7-Deazaadenines: The Influence of the 7-Substituent Chain Length and Charge on the Duplex Stability

Abstract

Oligonucleotides carrying alkynyl and aminoalkynyl chains at the position 7 of 7-deazaadenine are synthesized, and the chain lengths as well as the bulkiness of the substituents are varied. The corresponding nucleosides 1a – f are prepared from 7-deaza-2′-deoxy-7-iodoadenosine and the particular alkynes by the Pd0-catalyzed cross-coupling reaction. The nucleosides are converted to the phosphoramidites 2a – f, which are used in solid-phase oligonucleotide synthesis. The stability of the duplexes is determined by the Tm values and the thermodynamic data. Compared to adenine or the unsubstituted 7-deazaadenine, the incorporation of a 7-ethynyl chain in a 7-deazaadenine moiety increases the duplex stability significantly, while a dodecynyl residue or a bulky steroid moiety leads to a duplex destabilization. A 3-aminoprop-1-ynyl residue (see 1g) or a 5-aminopent-1-ynyl residue (see 1h), which are charged under neutral conditions, lead to zwitterionic DNA. A high density of charged residues as found in homomers impairs duplex formation, most probably by counter-ion condensation.