Duplex DNA and DNA RNA Hybrids with Parallel Strand Orientation: 2 `-Deoxy-2 `-fluoroisocytidine, 2 `-Deoxy-2 `-fluoroisoguanosine, and Canonical Nucleosides with 2 `-Fluoro Substituents Cause Unexpected Changes on the Double Helix Stability

Autor(en): Ingale, Sachin A.
Leonard, Peter
Quang Nhat Tran
Seela, Frank
Stichwörter: ANALOGS; ANTIPARALLEL CHAIN ORIENTATION; BASE-PAIRING PROPERTIES; Chemistry; Chemistry, Organic; DA-CENTER-DOT; ENZYMATIC INCORPORATION; FLUORINATED NUCLEOSIDES; ISOGUANINE; ISOGUANOSINE; NMR; OLIGONUCLEOTIDE DUPLEXES
Erscheinungsdatum: 2015
Herausgeber: AMER CHEMICAL SOC
Journal: JOURNAL OF ORGANIC CHEMISTRY
Volumen: 80
Ausgabe: 6
Startseite: 3124
Seitenende: 3138
Zusammenfassung: 
Oligonucleotides with parallel or antiparallel strand orientation incorporating 2'-fluorinated 2'-deoxyribonucleosides with canonical nucleobases or 2'-deoxy-2'-fluoroisocytidine ((F)iC(d), 1c) and 2'-deoxy-2'-fluoroisoguanosine (c, 3c) were synthesized. To this end, the nucleosides 1c and 3c as well as the phosphoramidite building blocks 19 and 23 were prepared and employed in solid-phase oligonucleotide synthesis. Unexpectedly, FiCd is not stable during oligonucleotide deprotection (55 degrees C, aq NH3) and was converted to a cyclonucleoside (14). Side product formation was circumvented when oligonucleotides were deprotected under mild conditions (aq ammoniaEtOH, rt). Oligonucleotides containing 2'-fluoro substituents (FiCd, (F)iC(d) and fluorinated canonical 2'-deoxyribonucleosides) stabilize double-stranded DNA, RNA, and DNA-RNA hybrids with antiparallel strand orientation. Unexpected strong stability changes are observed for oligonucleotide duplexes with parallel chains. While fluorinated oligonucleotides form moderately stable parallel stranded duplexes with complementary DNA, they do not form stable hybrids with RNA. Furthermore, oligoribonucleotide duplexes with parallel strand orientation are extremely unstable. It is anticipated that nucleic acids with parallel chains might be too rigid to accept sugar residues in the N-conformation as observed for ribonucleosides or 2'-deoxy-2'-fluororibonucleosides. These observations might explain why nature has evolved the principle of antiparallel chain orientation and has not used the parallel chain alignment.
ISSN: 00223263
DOI: 10.1021/acs.joc.5b00040

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