Warum pentose‐und nicht hexose‐nucleinsäuren? Teil III. Oligo(2′,3′‐dideoxy‐β‐D‐glucopyranosyl) nucleotide (‘homo‐DNS’): Paarungesigenschaften

Abstract

The paper presents results of a comprehensive investigation on the pairing properties of homo-DNA oligonucleotides, the preparation of which has been described in Part IIof this series [2]. The investigation was carried out by using established methods described in the literature for the characterization of oligonucleotides in the natural series, such as determination of melting temperatures of oligonucleotide duplexes by temperature-dependent UV spectrosocpy, determination of thermodynamic data of duplex formation from the concentration dependence of melting temperatures, determination of pairing stoichiometry by ratio-dependent UV spectroscopy of binary mixtures of pairing partners, temperature-dependent CD spectroscopy, gel electrophoresis under non-denaturing conditions, and -in selected cases -'H-and "P-NMR spectroscopy.The systematic comparison of the paring properties of homo-DNA oligonucleotides with corresponding DNA nucleotides (up to dodecamers) indicates that homo-DNA is a highly efficient, autonomous, artificial pairing system with a pairing behavior that is in part similar to, but also, in part, strikingly different from, the pairing behavior of DNA. The pairing properties established so far are listed below in a manner that reflects the sequence of subtitles in Chapt.2 of the text; they were determined under the conditions: H20, 0 . 1 5~ NaCI, 0 . 0 1~ Tris-HC1 buffer, pH 7, oligonucleotide concentrations in the ~L M range, 1 : 1 ratio of single strands in the case of non-selfcomplementary sequences.

New methylene-bridged hexopyranosyl nucleoside modified oligonucleotides (BHNA): synthesis and biochemical studies

“…13,17 (3) The AONs produced by the replacement of the pentofuranosyl sugar with the hexopyranosyl sugar 19 give thermodynamically stable duplexes with the target DNA or RNA. It is because, first, the sixmembered ring system adopt a rigid chair conformation, requiring a less negative entropy change during the duplex formation; and second, the interstrand phosphate distance in the six-membered pyranosyl-modified system is larger than in the natural nucleic acid duplexes giving a relatively less interstrand charge repulsion compared to the native counterpart.…”

Tuning Molecular Recognition of RNA and DNA via Sugar Modification

“…3B) for the stem part of MBs. Homo-DNA, a homologue of natural DNA, was shown before by Eschenmoser and coworkers to form stable, antiparallel duplexes with itself, without cross-pairing to natural DNA [21]. Moreover, homo-DNA can easily be prepared by standard automated phosphoramidite chemistry and is thus fully compatible with DNA synthesis [22].…”

Synthesis and Structure of New Methylene-Bridged Hexopyranosyl Nucleoside (BHNA)

“…Replacement of the pentofuranosyl sugar with hexopyranosyl sugar 24 however gives another type of conformationally-constrained nucleoside because the activation energy barrier for interconversion of conformers in the later is much higher than in the former.…”

“…24 It is because, first, the six-membered ring system adopts a rigid chair conformation, requiring a less negative entropy change during the duplex formation; and second, the interstrand phosphate distance in the six-membered pyranosyl-modified system is larger than in the natural nucleic acid duplexes, giving a relatively less interstrand charge repulsion compared to the native counterpart. 25 Many different types of hexopyranosyl nucleosides have been so far synthesized by the groups of Herdewijn 9 and Eschenmoser.…”

“…25 Many different types of hexopyranosyl nucleosides have been so far synthesized by the groups of Herdewijn 9 and Eschenmoser. 25 These hexopyranosyl nucleosides have also been incorporated in to oligonucleotides, and their affinity toward complementary RNA or DNA, as well as their biochemical features have been studied: oligonucleotides composed of dideoxyglycopyranosyl-4',6'-nucleoside (homo-DNA, Figure 1) is almost linear, and not able to form duplexes with either RNA or DNA, 25,26 while oligonucleotides with 1',5'-anhydrohexitol nucleoside (HNA, Figure 1), 27,28 cyclohexanyl nucleoside (CNA, Figure 1) 29 or cyclohexenyl nucleoside (CeNA, Figure 1) [30][31][32] modification have improved affinity toward RNA and show improved nuclease resistance compared to the native counterpart. Amongst these, CeNA modified oligonucleotides have attracted more attention because they are able to activate RNase H, resulting in cleavage of the RNA strand in the DNA-RNA heteroduplexes.…”