Solution structure of a HNA–RNA hybrid

Lescrinier, Eveline; Esnouf, Robert; Schraml, Jan; Busson, Roger; Heus, Hans A.; Hilbers, C. W.; Herdewijn, Piet

doi:10.1016/s1074-5521(00)00017-x

Cited by 76 publications

(86 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To overcome these obstacles, a variety of chemically modified oligonucleotides have been proposed. DNA analogues showing interesting properties in terms of nuclease stability, target affinity, and low cytotoxicity are peptide nucleic acid (10 -15), N5 ¶/P5 ¶ phosphoramidites (16), morpholino phosphoramidites (17), and hexitol nucleic acids (18,19). In addition, locked nucleic acids (LNA) have been proposed as antisense molecules of enhanced properties (20,21).…”

Section: Introductionmentioning

confidence: 99%

Antisense locked nucleic acids efficiently suppress BCR/ABL and induce cell growth decline and apoptosis in leukemic cells

Rapozzi

Cogoi²,

Xodo³

2006

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Chronic myeloid leukemia (CML) develops when a hematopoietic stem cell acquires the Philadelphia chromosome carrying the BCR/ABL fusion gene. This gives the transformed cells a proliferative advantage over normal hematopoietic cells. Silencing the BCR/ABL oncogene by treatment with specific drugs remains an important therapeutic goal. In this work, we used locked nucleic acid (LNA) -modified oligonucleotides to silence BCR/ABL and reduce CML cell proliferation, as these oligonucleotides are resistant to nucleases and exhibit an exceptional affinity for cognate RNA. The anti-BCR/ABL oligonucleotides were designed as LNA-DNA gapmers, consisting of end blocks of 3/4 LNA monomers and a central DNA stretch of 13/14 deoxyribonucleotides. The gapmers were complementary to the b2a2 and b3a2 mRNA junctions with which they form hybrid duplexes that have melting temperatures of 79°C and 75°C, respectively, in a 20 mmol/L NaCl-buffered (pH 7.4) solution. Like DNA, the designed LNA-DNA gapmers were capable of activating RNase H and promote cleavage of the target b2a2 and b3a2 BCR/ABL mRNAs. The treatment of CML cells with junction-specific antisense gapmers resulted in a strong and specific reduction of the levels of BCR/ABL transcripts (f20% of control) and protein p210 BCR/ABL

show abstract

Section: Introductionmentioning

confidence: 99%

Antisense locked nucleic acids efficiently suppress BCR/ABL and induce cell growth decline and apoptosis in leukemic cells

Rapozzi

Cogoi²,

Xodo³

2006

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

show abstract

“…Interconversion between chair conformations is possible energetically, and this has been experimentally demonstrated for the iodouracil congener when complexed with viral thymidine kinase (TK). [22] However, both at the monomeric level [1,2] and at the oligomeric level, [9,15,23] the hexitol nucleosides adopt conformations with an axially oriented base moiety.…”

mentioning

confidence: 99%

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

et al. 1999

View full text Add to dashboard Cite

nucleic acids are RNA-selective. l-CNA hybridizes either very weakly or not at all with natural nucleic acids, and the nature of this association is not clear. This study of CNAs leads us to hypothesize that a) the conformation of a single nucleoside analogue may be different from its conformation in an oligonucleotide and b) the conformational stress of a nucleotide analogue incorporated in an oligomer may contribute to the sequence-dependent thermal stability of oligonucleotide complexes.

show abstract

“…Pyranose nucleic acids form quasi-linear structures, [19,20] while hexitol nucleic acids adopt A-form helical conformations. [7,9,21] The former oligomers do not hybridise with natural nucleic acids, while the latter oligonucleotides have the potential to do so. The influence of supplementary hydroxy groups introduced on the six-membered carbohydrate moiety is, therefore, different in both systems.…”

Section: Discussionmentioning

confidence: 99%

“…Oligomers E and F ( Figure 4) were evaluated for their serum stability in 90 % of human serum. Oligomer (dA) 21 was used as internal standard. After incubation at 37 8C, serum samples were extracted by anion-exchange centrifugal membranes, desalted by drop analysis and analysed by MECC.…”

mentioning

confidence: 99%

D-Altritol Nucleic Acids (ANA): Hybridisation Properties, Stability, and Initial Structural Analysis

Allart

Khan

Rosemeyer

et al. 1999

Chemistry - A European Journal

View full text Add to dashboard Cite

Oligonucleotides composed of a phosphorylated d-altritol backbone with nucleobases introduced in the 2'-position, hybridise strongly and sequence-selectively with RNA in an antiparallel way. The order of hybridisation strength is: dsANA b ANA:RNA b ANA:DNA. Complexes between ANA and RNA or DNA are more stable than between HNA and natural oligonucleotides. The dsANA hybrid is extremely stable. When compared with an identical dsDNA sequence, the DT m per modification is 10.2 8C for a hexamer. CD spectral analysis indicates that ANA complexes are very similar to the A-form dsRNA duplex. ANA are stable in alkaline medium up to pH 12 and, likewise, are not degraded in human serum.

show abstract

Solution structure of a HNA–RNA hybrid

Cited by 76 publications

References 41 publications

Antisense locked nucleic acids efficiently suppress BCR/ABL and induce cell growth decline and apoptosis in leukemic cells

Antisense locked nucleic acids efficiently suppress BCR/ABL and induce cell growth decline and apoptosis in leukemic cells

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

D-Altritol Nucleic Acids (ANA): Hybridisation Properties, Stability, and Initial Structural Analysis

Contact Info

Product

Resources

About