pH‐Independent Recognition of the dG ⋅ dC Base Pair in Triplex DNA: 9‐Deazaguanine N 7 ‐(2′‐Deoxyribonucleoside) and Halogenated Derivatives Replacing Protonated dC

• Published in: Helvetica chimica acta 2006-04, Vol.89 (4), p.598-613
• Main Authors: Seela, Frank, Shaikh, Khalil I., Wiglenda, Thomas
• Format: Article
• Language: English
• ISSN: 0018-019X; 1522-2675
• DOI: 10.1002/hlca.200690063

Triplex‐forming oligonucleotides (TFOs) containing 9‐deazaguanine N 7 ‐(2′‐deoxyribonucleoside) 1a and halogenated derivatives 1b,c were synthesized employing solid‐phase oligonucleotide synthesis. For that purpose, the phosphoramidite building blocks 5a – c and 8a – c were synthesized. Multiple incorporations of 1a – c in place of dC were performed within TFOs, which involved the sequence of five consecutive 1a – c  ⋅ dG ⋅ dC triplets as well as of three alternating 1a – c  ⋅ dG ⋅ dC and dT ⋅ dA ⋅ dT triplets. These TFOs were designed to bind in a parallel orientation to the target duplex. Triplex forming properties of these oligonucleotides containing 1a – c in the presence of Na + and Mg 2+ were studied by UV/melting‐curve analysis and confirmed by circular‐dichroism (CD) spectroscopy. The oligonucleotides containing 1a in the place of dC formed stable triplexes at physiological pH in the case of sequence of five consecutive 1a  ⋅ dG ⋅ dC triplets as well as three alternating 1a – c  ⋅ dG ⋅ dC and dT ⋅ dA ⋅ dT triplets. The replacement of 1a by 9‐halogenated derivatives 1b,c further enhanced the stability of DNA triplexes. Nucleosides 1a – c also stabilized duplex DNA.