287737-39-7Relevant academic research and scientific papers
Synthesis of 2′,4′-propylene-bridged (Carba-ENA) thymidine and its analogues: The engineering of electrostatic and steric effects at the bottom of the minor groove for nuclease and thermodynamic stabilities and elicitation of RNase H
Liu, Yi,Xu, Jianfeng,Karimiahmadabadi, Mansoureh,Zhou, Chuanzheng,Chattopadhyaya, Jyoti
supporting information; experimental part, p. 7112 - 7128 (2010/12/25)
2′,4′-Propylene-bridged thymidine (carba-ENA-T) and five 8′-Me/NH2/OH modified carba-ENA-T analogues have been prepared through intramolecular radical addition to C=N of the tethered oxime-ether. These carba-ENA nucleosides have been subsequently incorporated into 15mer oligodeoxynucleotides (AON), and their affinity toward cDNA and RNA, nuclease resistance, and RNase H recruitment capability have been investigated in comparison with those of the native and ENA counterparts. These carba-ENAs modified AONs are highly RNA-selective since all of them led to slight thermal stabilization effect for the AON:RNA duplex, but quite large destabilization effect for the AON:DNA duplex. It was found that different C8′ substituents (at the bottom of the minor groove) on carba-ENA-T only led to rather small variation of thermal stability of the AON:RNA duplexes. We, however, observed that the parent carba-ENA-T modified AONs exhibited higher nucleolytic stability than those of the ENA-T modified counterparts. The nucleolytic stability of carba-ENA-T modified AONs can be further modulated by C8′ substituent to variable extents depending on not only the chemical nature but also the stereochemical orientation of the C8′ substituents: Thus, (1) 8′S-Me on carba-ENA increases the nucleolytic stability but 8′R-Me leads to a decreased effect; (2) 8′R-OH on carba-ENA had little, if any, effect on nuclease resistance but 8′S-OH resulted in significantly decreased nucleolytic stability; and (3) 8′-NH2 substituted carba-ENA leads to obvious loss in the nuclease resistance. The RNA strand in all of the carba-ENA derivatives modified AON:RNA hybrid duplexes can be digested by RNase H1 with high efficiency, even at twice the rate of those of the native and ENA modified counterpart.
Synthesis and properties of 2′-O,4′-C-ethylene-bridged nucleic acids (ENA) as effective antisense oligonucleotides
Morita, Koji,Takagi, Miho,Hasegawa, Chikako,Kaneko, Masakatsu,Tsutsumi, Shinya,Sone, Junko,Ishikawa, Tomio,Imanishi, Takeshi,Koizumi, Makoto
, p. 2211 - 2226 (2007/10/03)
Novel bicyclo nucleosides, 2′-O,4′-C-ethylene nucleosides and 2′-O,4′-C-propylene nucleosides, were synthesized as building blocks for antisense oligonucleotides to further optimize the 2′-O,4′-C-methylene-linkage of bridged nucleic acids (2′,4′-BNA) or l
2′-O,4′-C-ethylene-bridged nucleic acids (ENA): Highly nuclease-resistant and thermodynamically stable oligonucleotides for antisense drug
Morita, Koji,Hasegawa, Chikako,Kaneko, Masakatsu,Tsutsumi, Shinya,Sone, Junko,Ishikawa, Tomio,Imanishi, Takeshi,Koizumi, Makoto
, p. 73 - 76 (2007/10/03)
To develop antisense oligonucleotides, novel nucleosides, 2′-O,4′-C-ethylene nucleosides and their corresponding phosphoramidites, were synthesized as building blocks. The 1H NMR analysis showed that the 2′-O,4′-C-ethylene linkage of these nucleosides restricts the sugar puckering to the N-conformation as well as the linkage of 2′-O,4′-C-methylene nucleosides which are known as bridged nucleic acids (BNA) or locked nucleic acids (LNA). The ethylene-bridged nucleic acids (ENA) showed a high binding affinity for the complementary RNA strand (ΔTm = + 5.2 °C/modification) and were more nuclease-resistant than natural DNA and BNA/LNA. These results indicate that ENA have better properties as antisense oligonucleotides than BNA/LNA.
