117626-97-8Relevant articles and documents
Metal-containing oligonucleotides: Solid-phase synthesis and luminescence properties [12]
Hurley,Tor
, p. 2194 - 2195 (1998)
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Synthesis of Phosphoramidite Monomers Equipped with Complementary Bases for Solid-Phase DNA Oligomerization
Romero-Pérez, Sonia,López-Martín, Isabel,Martos-Maldonado, Manuel C.,Somoza, álvaro,González-Rodríguez, David
, p. 41 - 45 (2020/01/03)
We describe the preparation of two monomers that bear complementary nucleobases at the edges (guanine-2′-deoxycytidine and 2-aminoadenine-2′-deoxyuridine) and that are conveniently protected and activated for solid-phase automated DNA synthesis. We report the optimized synthetic routes leading to the four nucleobase derivatives involved, their cross-coupling reactions into dinucleobase-containing monomers, and their oligomerization in the DNA synthesizer.
Increasing the Stability of DNA:RNA Duplexes by Introducing Stacking Phenyl-Substituted Pyrazole, Furan, and Triazole Moieties in the Major Groove
Hornum, Mick,Kumar, Pawan,Podsiadly, Patricia,Nielsen, Poul
supporting information, p. 9592 - 9602 (2015/10/12)
Consecutive incorporations of our previously published thymidine analogue, 5-(1-phenyl-1H-1,2,3-triazol-4-yl)-2′-deoxyuridine monomer W in oligonucleotides, has demonstrated significant duplex-stabilizing properties due to its efficient staking properties in the major groove of DNA:RNA duplexes. The corresponding 2′-deoxycytidine analogue is not as well-accommodated in duplexes, however, due to its clear preference for the ring-flipped coplanar conformation. In our present work, we have used ab initio calculations to design two new building blocks, 5-(5-phenylfuran-2-yl)-2′-deoxycytidine monomer Y and 5-(1-phenyl-1H-pyrazol-3-yl)-2′-deoxycytidine monomer Z, that emulate the conformation of W. These monomers were synthesized by Suzuki-Miyaura couplings, and the pyrazole moiety was obtained in a cycloaddition from N-phenylsydnone. We show that the novel analogues Y and Z engage in efficient stacking either with themselves or with W due to a better overlap of the aromatic moieties. Importantly, we demonstrate that this translates into very thermally stable DNA:RNA duplexes, thus making Y and especially Z good candidates for improving the binding affinities of oligonucleotide-based therapeutics. Since we now have both efficiently stacking T and C analogues in hand, any purine rich stretch can be effectively targeted using these simple analogues. Notably, we show that the introduction of the aromatic rings in the major groove does not significantly change the helical geometry.
