Publication Date:
2015-07-12
Description:
A triplex-forming oligonucleotide (TFO) could be a useful molecular tool for gene therapy and specific gene modification. However, unmodified TFOs have two serious drawbacks: low binding affinities and high sequence-dependencies. In this paper, we propose a new strategy that uses a new set of modified nucleobases for four-base recognition of TFOs, and thereby overcome these two drawbacks. 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 C s ), d g C and 4S-(2-guanidoethyl)-4-thiothymidine ( gs T). Further, we observed that N-acetyl-2,7-diamino-1,8-naphtyridine ( DA N ac ) 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 N ac , 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. To the best of our knowledge, this is the first report in which a fully modified TFO accurately recognizes a complementary DNA duplex having a mixed sequence under neutral conditions.
Print ISSN:
0305-1048
Electronic ISSN:
1362-4962
Topics:
Biology
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