Synthesis and Pairing Properties of Oligonucleotides Containing 3-Hydroxy-4-hydroxymethyl-1-cyclohexanyl Nucleosides

Bicyclo[3.2.1]amide-DNA: A Chiral, Nonchiroselective Base-Pairing System

“…It has also been shown that oligo‐homothymidylates of the RNA analogue LNA can bind to complementary l ‐ RNA, forming enantiomorphic duplex structures 26. The cyclohexanyl DNA analogue CNA (the carba analogue of the hexitol nucleic acid analogue HNA) forms heterochiral duplexes in its own series (homo‐A/homo‐T strands) but not with DNA and RNA 5. The same feature is known for the RNA isomer pRNA, which can form heterochiral duplexes within its backbone type in a non‐natural base‐context,27 but typically has a strong preference for homochiral duplex formation 28…”

“…Major changes in the association behavior of oligonucleotides arise, as expected, from variation of the ribofuranose substructure in DNA and RNA. In this context, six‐membered ring versions (e.g, homo‐DNA,2 HNA,3 CeNA,4 CNA,5 p‐RNA6) and four‐membered ring versions (e.g, carbocyclic oxetanocine‐DNA7 and cyclobutane‐DNA8), as well as ring‐deficient analogues (such as seco ‐DNA9, 10 and glycerol ‐ DNA11) have been evaluated. Besides this, analogues of increased (seven bonds)7 or decreased (five bonds)12 length in the repetitive backbone unit have been evaluated.…”

Oligonucleotides containing a ribo-configured cyclohexanyl nucleoside: probing the role of sugar conformation in base pairing selectivity

“…6 One of the most renowned examples of sugar-modified nucleic acids is represented by the oligonucleotide system composed of (6′ → 4′)linked 1′,5′-anhydro-D-arabino-hexitol nucleotides 7 (HNA, Hexitol Nucleic Acids; Fig. 2 The analysis of the physicochemical properties of oligonucleotide systems composed of pyranyl (α-HNA, 8 ANA, 9 MNA, F-HNA, 10 cANA 11 ), pyranosyl (homoDNA, 12 MANA, 13 DMANA 14 ) and carbocyclic (CNA, 15 CeNA, 16 F-CeNA 17 ) nucleotides, quite often evaluated in both enantiomeric forms, 15,[18][19][20] has led to the identification of HNA congeners endowed with even superior hybridization properties, 9,10,13,16 thus acting, along with HNA, as excellent candidates for applications in therapy, 21 diagnostics 22 and chemical genetics. As widely reported, the strong and selective affinity for RNA (ΔT m /mod up to +3°C) relies on a pre-organized conformation of the non-hydrolyzable hexitol ring, closely resembling the C3′-endo sugar ring pucker of natural ribonucleotides.…”

TNA as a Potential Alternative to Natural Nucleic Acids

“…However, the absence of cross‐pairing between pRNA and RNA does not preclude the possibility of pRNA being an ancestor of RNA, but only suggests that it is very unlikely. A nucleic acid that can adopt several conformations and that in this way can hybridize equally with pRNA and RNA, might be considered as an evolutionary intermediate between them 5…”