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pH-Independent Recognition of the dG ⋅ dC Base Pair in Triplex DNA: 9-Deazaguanine N7-(2′-Deoxyribonucleoside) and Halogenated Derivatives Replacing Protonated dC

✍ Scribed by Frank Seela; Khalil I. Shaikh; Thomas Wiglenda


Publisher
John Wiley and Sons
Year
2006
Tongue
German
Weight
167 KB
Volume
89
Category
Article
ISSN
0018-019X

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✦ Synopsis


Abstract

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 5ac and 8ac were synthesized. Multiple incorporations of 1ac in place of dC were performed within TFOs, which involved the sequence of five consecutive 1ac ⋅ dG ⋅ dC triplets as well as of three alternating 1ac ⋅ 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 1ac 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 1ac ⋅ 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 1ac also stabilized duplex DNA.