Parallel-stranded oligonucleotide duplexes containing 5-methylisocytosine-guanine and isoguanine-cytosine base pairs

Abstract

Parallel-stranded oligonucleotides containing 5-methylisocytosine-guanine and/or isoguanine-cytosine base pairs were prepared. The coupling efficiency was higher than 99% when the phosphoramidites of 2'-deoxy-5-methylisocytidine (2a) and of 2'-deoxyisoguanosine (3) were employed in solid-phase synthesis. The glycosylic bond of 2'-deoxy-5-methylisocytidine (1a) is stabilized against acid in the case of the amidine derivatives 4a, b. Depyrimidination occurs upon extended exposure to ammonia. The orientation bf the parallel-stranded (ps) duplexes was unambiguously determined using the pyrene excimer fluorescence. The antiparallel (aps) duplex d(A(12)). d(T-12) (25 . 26) turned into the parallel orientation when two central adenine-thymine base pairs were replaced by isoguanine-cytosine pairs. The thermal stability of ps-duplexes containing 5-methylisocytosine-guanine base pairs was found to be significantly lower than that of duplexes with isoguanine-cytosine pairs. According to the CD spectra, ps-DNA-DNA or DNA-RNA hybrids show differences in their secondary structures compared to their aps counterparts. (C) 1999 Elsevier Science Ltd. All rights reserved.