1,5‐Anhydrohexitol Nucleic Acids, a New Promising Antisense Construct

Abstract

For corrigendum see DOI:

Hybridization potential of oligonucleotides comprising 3′-O-methylated altritol nucleosides

“…It has been documented that single modified ONs when incorporated into natural nucleic acids may induce local geometry changes over several neighboring base pairs. Strong hybridizing complexes were obtained, indicating a pre-organized structure fitting the A-type dsRNA duplex [10]. Remarkably, the higher affinity obtained is relatively Fig.…”

“…Samples were infused at 3µL/min and spectra were obtained in positive (or: negative) ionization mode with a resolution of 15000 (FWHM) using leucine enkephalin as lock mass. Synthesis of HNA and ANA monomers was outlined before [10,30]. Assembly of ANA and HNA constructs likewise has been described previously [11,12].…”

“…Another way to address this problem is to assemble carbohydrate-modified ONs, exemplified by hexitol nucleic acids [10][11][12][13][14], 2'-O-(2-methoxy)ethyl ONs [15,16] and bicyclic ONs [17], with the LNA monomers of the Wengel group [18] showing the strongest affinity for RNA, and having many alternative structures [19]. The strong hybridization characteristics between these structures and complementary RNA are generally attributed to the formation of a preorganized conformation, fitting the A-form of dsRNA, with strong stacking interactions between the bases, adequate interaction of the latter in a Watson-Crick type geometry with their complement, and efficient hydration of the double-stranded helix [20].…”

Disulphide Bond Containing Oligodeoxynucleotide Stabilizes DNA:RNA Duplex Structure

“…The C-5 propyne analogs of 2'-deoxycytidine significantly enhanced the affinity to double helix formation with single strand RNA, relative to thymidine and 5-methyl-2-deoxycytidine 18 . To improve the affinity of single strand ligand towards single strand RNA various other successful modifications have been carried out in the past [19][20][21][22][23][24][25][26][27] . Recent candidates of such chemically modified oligonucleotide analogs include HNA 28 , locked nucleic acid (LNA) 29,30 , 2′-MOE-RNA and related 2′-O-modified RNA 31 , PNA and modifications thereof 32 , Morpholino-NAs 33 and tricyclo-DNA [34][35][36] .…”

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

“…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.…”