Synthesis and triplex-forming properties of oligonucleotides capable of recognizing corresponding DNA duplexes containing four base pairs.
Bottom Line: TFOs containing a 2'-deoxy-4N-(2-guanidoethyl)-5-methylcytidine (d(g)C) residue for a C-G base pair have higher binding and base recognition abilities than those containing 2'-OMe-4N-(2-guanidoethyl)-5-methylcytidine (2'-OMe (g)C), 2'-OMe-4N-(2-guanidoethyl)-5-methyl-2-thiocytidine (2'-OMe (g)Cs), d(g)C and 4S-(2-guanidoethyl)-4-thiothymidine ((gs)T).Further, we observed that N-acetyl-2,7-diamino-1,8-naphtyridine ((DA)Nac) has a higher binding and base recognition abilities for a T-A base pair compared with that of dG and the other DNA derivatives.On the basis of this knowledge, we successfully synthesized a fully modified TFO containing (DA)Nac, d(g)C, 2'-OMe-2-thiothymidine (2'-OMe (s)T) and 2'-OMe-8-thioxoadenosine (2'-OMe (s)A) with high binding and base recognition abilities.
Affiliation: Department of Life Science, Tokyo Institute of Technology, 4259 Nagatsuta, Yokohama 226-8501, Japan email@example.com.Show MeSH
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Mentions: Finally, synthesis of the fully modified TFO 10 containing DANac, dgC, 2’-OMesT and 2’-OMesA was carried out to measure the binding and base recognition of the fully modified TFO to HP DNAs 5–13 with the mixed sequences. Although we previously reported synthesis of the 2’-OMesA containing a benzoyl group as a protecting group, it was observed that the DANac moieties were decomposed under the conditions for deprotection of the N-benzoyl group (treatment with 28% NH4OH for 8 h). Therefore, a phenoxyacetyl group, which can be easily cleaved under mild conditions compared with a benzoyl group, was introduced into the amino group of 2’-O-methyl-8-(2-trimethylsilylethylthio)adenosine 23 in the presence of trimethylsilyl chloride, as shown in Scheme 6. After tritylation of the 5’-hydroxy group, the 3’-phosphitylation was carried out to give the 2’-OMesA phosphoramidite unit 26.
Affiliation: Department of Life Science, Tokyo Institute of Technology, 4259 Nagatsuta, Yokohama 226-8501, Japan firstname.lastname@example.org.