Biological activity of hexitol nucleic acids targeted at Ha-ras and intracellular adhesion molecule-1 mRNA

Vandermeeren, Marc; Prévéral, Sandra; Janssens, Sophie; Geysen, Johan; Saison-Behmoaras, E.; Herdewijn, Piet

doi:10.1016/s0006-2952(99)00367-6

Cited by 25 publications

(22 citation statements)

References 21 publications

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“…We observed that the increase in Tm per modification of an HNA:RNA duplex versus duplexes of natural nucleic acids is sequence and length dependent [22]. HNA is an efficient steric-blocking agent, as observed during investigations of HNA in cell free translation experiments (giving IC50 values of 50 nM as inhibitors of Ha-ras mRNA translation) [23].…”

Section: Introductionsupporting

confidence: 52%

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

2012

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Abstract:A series of 3'-O-methylated D-altrohexitol nucleoside analogs (MANA) was synthesized comprising all four base moieties, adenine, cytosine, uracil and guanine. These monomers were incorporated into While the specificity of these new synthons is slightly lower compared to mismatches within RNA double strands, it is similar to the discrimination potential of other hexitol modifications (HNA and ANA) which already proved their biologic interest, highlighting the potential of MANA constructs in antisense and in siRNA applications.3

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Section: Introductionsupporting

confidence: 52%

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

2012

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“…Due to this preorganization, HNA is an efficient template for nonenzymatic synthesis of RNA. The potential of HNAs as antisense oligonucleotides has recently been described [44]. When considering the minor-groove structure of a HNA´RNA duplex, we observed a large difference in the polarity of the solvent-accessible surface between the RNA and HNA flanks.…”

Section: Ana´rnamentioning

confidence: 69%

Molecular-Dynamics Studies of Single-Stranded Hexitol, Altritol, Mannitol, and Ribose Nucleic Acids (HNA, MNA, ANA, and RNA, Resp.) and of the Stability of HNA⋅RNA, ANA⋅RNA, and MNA⋅RNA Duplexes

Froeyen

Wroblowski

Esnouf

et al. 2000

HCA

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Dedicated to Professor Albert Eschenmoser on the occasion of his 75th birthdayThe influence of the orientation of a 3'-OH group on the conformation and stability of hexitol oligonucleotides in complexes with RNA and as single strands in aqueous solution was investigated by molecular-dynamics (MD) simulations with AMBER 4.1. The particle mesh Ewald (PME) method was used for the treatment of long-range electrostatic interactions. An equatorial orientation of the 3'-OH group in the single-stranded d-mannitol nucleic acid (MNA) m(GCGTAGCG) and in the complex with the RNA r(CGCAUCGC) has an unfavorable influence on the helical stability. Frequent H-bonds between the 3'-OH group and the OÀC(6') of the phosphate backbone of the following nucleotide explain the distorted conformation of the MNA´RNA complex as well as that of the single MNA strand. This is consistent with experimental results that show lowered hybridization potentials for MNA´RNA complexes.An axial orientation of the 3'-OH group in the d-altritol nucleic acid (ANA) a(GCGTAGCG) leads to a stable complex with the complementary RNA r(CGCAUCGC), as well as to a more highly preorganized singlestranded ANA chain. The averaged conformation of the ANA´RNA complex is similar to that of A-RNA, with only minor changes in groove width, helical curvature, and H-bonding pattern. The relative stabilities of ANAŔ NA vs. HNA´RNA (HNA d-hexitol nucleic acid without 3'-OH group) can be explained by differences in restricted movements, H-bonds, and solvation effects.

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“…In the derivatives which are based on α-anomeric nucleosides [41], hexitol-nucleic acids [42], 2' O-alkylated ribonucleosides [43,44] and carba-DNA [45,46] the modification effects, in particular, an increased stability. By freezing the binding conformation methanocarba-DNA [47] is obtained.…”

Section: Chemically Modified Oligonucleotidesmentioning

confidence: 99%

Scintigraphic Imaging of Gene Expression and Gene Transfer

Haberkorn¹,

Mier²,

Eisenhut

2005

CMC

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Assessment of gene function following the completion of human genome sequencing can be performed with nuclear medicine procedures. These techniques may be applied for the determination of gene function and regulation using established and new tracers or using in vivo reporter genes such as genes encoding enzymes, receptors, antigens, or transporters. Visualization of in vivo reporter gene expression can be done using radiolabeled substrates, antibodies, or ligands. Combinations of specific promoters and in vivo reporter genes may deliver information about the regulation of the corresponding genes. The role of radiolabeled antisense molecules for the analysis of mRNA content has to be investigated. However, possible applications are therapeutic interventions using triplex oligonucleotides with therapeutic isotopes, which can be brought near to specific DNA sequences to induce DNA strand breaks at selected loci. Imaging of labeled siRNA's makes sense if these are used for therapeutic purposes in order to assess the delivery of these new drugs to their target tissue. Pharmacogenomics will identify new surrogate markers for therapy monitoring which may represent potential new tracers for imaging.

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Biological activity of hexitol nucleic acids targeted at Ha-ras and intracellular adhesion molecule-1 mRNA

Cited by 25 publications

References 21 publications

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

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

Molecular-Dynamics Studies of Single-Stranded Hexitol, Altritol, Mannitol, and Ribose Nucleic Acids (HNA, MNA, ANA, and RNA, Resp.) and of the Stability of HNA⋅RNA, ANA⋅RNA, and MNA⋅RNA Duplexes

Scintigraphic Imaging of Gene Expression and Gene Transfer

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