A1 Refereed original research article in a scientific journal
Metal-Ion-Mediated Base Pairing between Natural Nucleobases and Bidentate 3,5-Dimethylpyrazolyl-Substituted Purine Ligands.
Authors: Taherpour Sharmin, Golubev Oleg, Lönnberg Tuomas
Publication year: 2014
Journal: Journal of Organic Chemistry
Journal name in source: The Journal of organic chemistry
Journal acronym: J Org Chem
Volume: 79
Issue: 19
First page : 8990
Last page: 8999
Number of pages: 10
ISSN: 1520-6904
DOI: https://doi.org/10.1021/jo501237r(external)
Abstract
The potential of three modified purine bases, namely, 6-(3,5-dimethylpyrazol-1-yl)purine, 2-(3,5-dimethylpyrazol-1-yl)hypoxanthine, and 2-(3,5-dimethylpyrazol-1-yl)adenine, for metal-ion-mediated base pairing within an oligonucleotide environment has been investigated. The respective modified nucleosides were incorporated in the middle of 9-mer 2'-O-methyl oligonucleotides and the hybridization of these modified oligonucleotides with their unmodified counterparts studied by UV and CD spectrometry in the absence and presence of Cu(2+) or Zn(2+). All of the modified oligonucleotides formed more stable duplexes in the presence of divalent metal ions than in the absence thereof, but with different preferences for the complementary oligonucleotide. The oligonucleotide incorporating 2-(3,5-dimethylpyrazol-1-yl)hypoxanthine readily accepted any of the natural nucleobases opposite to this modified base regardless of whether Cu(2+) or Zn(2+) was used as the bridging metal ion. The other two oligonucleotides, on the other hand, were much more discriminating, exhibiting markedly elevated Tm values only in the presence of Cu(2+) and only when certain natural nucleobases were paired with the modified one. The origin of the selectivity (or promiscuity) of the metal-ion-mediated base pairing is discussed in terms of the ability of the modified nucleobases, as well as their natural counterparts, to serve as anionic ligands.
The potential of three modified purine bases, namely, 6-(3,5-dimethylpyrazol-1-yl)purine, 2-(3,5-dimethylpyrazol-1-yl)hypoxanthine, and 2-(3,5-dimethylpyrazol-1-yl)adenine, for metal-ion-mediated base pairing within an oligonucleotide environment has been investigated. The respective modified nucleosides were incorporated in the middle of 9-mer 2'-O-methyl oligonucleotides and the hybridization of these modified oligonucleotides with their unmodified counterparts studied by UV and CD spectrometry in the absence and presence of Cu(2+) or Zn(2+). All of the modified oligonucleotides formed more stable duplexes in the presence of divalent metal ions than in the absence thereof, but with different preferences for the complementary oligonucleotide. The oligonucleotide incorporating 2-(3,5-dimethylpyrazol-1-yl)hypoxanthine readily accepted any of the natural nucleobases opposite to this modified base regardless of whether Cu(2+) or Zn(2+) was used as the bridging metal ion. The other two oligonucleotides, on the other hand, were much more discriminating, exhibiting markedly elevated Tm values only in the presence of Cu(2+) and only when certain natural nucleobases were paired with the modified one. The origin of the selectivity (or promiscuity) of the metal-ion-mediated base pairing is discussed in terms of the ability of the modified nucleobases, as well as their natural counterparts, to serve as anionic ligands.