14057-65-9Relevant academic research and scientific papers
Synthesis and stability of a 2′-O-[N-(aminoethyl)carbamoyl] methyladenosine-containing dinucleotide
Milton, Stefan,Ander, Charlotte,Honcharenko, Dmytro,Honcharenko, Malgorzata,Yeheskiely, Esther,Stroemberg, Roger
, p. 7184 - 7192 (2013/11/06)
Working towards the synthesis of 2′-O-[N-(aminoethyl)carbamoyl] methyl-modified di- and oligonucleotides, we have synthesised a protected 2′-O-[N-(aminoethyl)carbamoyl]methyl-modified adenosine where the modification is introduced in a convenient one-pot three-step procedure. The corresponding H-phosphonate building block was also synthesised, and from this intermediate, a 2′-O-[N-(aminoethyl)carbamoyl]methyl-containing dinucleotide could be made. We also performed studies on the chemical and enzymatic stability of this dinucleotide. The dinucleotide was subjected to different ammonolysis and other basic conditions, and HPLC analysis showed that the modification was intact to most conditions, but that there was some minor hydrolysis when NH3 (concd. aq.) was used at 55 °C. Under several other sets of conditions, including saturated NH3 in methanol, and ethylenediamine, the amide remained intact. Treatment of the dinucleotide with Phosphodiesterase I from Crotalus adamanteus venom and Phosphodiesterase II from bovine spleen showed that the N-(aminoethyl)carbamoylmethyl moiety gives the phosphodiester linkage substantial protection against enzymatic degradation; the phosphodiester was not degraded by PDE II at all after seven days. A 2′-O-[N-(aminoethyl)carbamoyl]methyl-modified adenosine and a corresponding dinucleotide were synthesised. Hydrolysis (1-2 %) was observed in concentrated aqueous NH3 at 55°C, but under several other sets of reaction conditions, the amide remained intact. The N-(aminoethyl) carbamoylmethyl moiety gave substantial protection against enzymatic degradation by nucleases from snake venom and bovine spleen. Copyright
Kinetic and Theoretical Studies on the Mechanism of Alkaline Hydrolysis of DNA
Takeda, Naoya,Shibata, Masahiko,Tajima, Nobuo,Hirao, Kimihiko,Komiyama, Makoto
, p. 4391 - 4396 (2007/10/03)
The reaction mechanism of alkaline hydrolysis of DNA has been investigated by kinetic analysis and density-functional-theory calculation. The rates of hydrolysis of thymidine 3′-monophosphate esters (including thymidylyl(3′-5′)thymidine (Tp-OT)) monotonically decrease as the leaving groups get poorer. According to the theoretical calculation in which the solvent effects are incorporated, no intermediate is formed in the course of the reaction. In the alkaline hydrolysis of the activated Tp-OT analogues having good leaving groups, the 3′,5′-cyclic monophosphate of thymidine is concurrently formed through the intramolecular attack by the 5′-alkoxide ion. In the hydrolysis of the native dinucleotide, however, this side reaction does not occur, since the transition state leading to the departure of its poor leaving group cannot be formed due to conformational restraint. These arguments are supported by the theoretical analysis on the hydrolysis of both dimethyl phosphate and its O(bridging)→S substituted analogue.
A New Approach for Chemical Phosphorylation of Oligonucleotides at the 5'-Terminus
Guzaev, Andrei,Salo, Harri,Azhayev, Alex,Loennberg, Harri
, p. 9375 - 9384 (2007/10/02)
A new efficient method for chemical 5'-phosphorylation of synthetic oligonucleotides is described.Accordingly, 2-cyanoethyl 3-(4,4'-dimethoxytrityloxy)-2,2-di(ethoxycarbonyl)propyl-1 N,N-diisopropyl phosphoramidite (1) was introduced as the 5'-terminal bu
EFFECT OF NUCLEOPHILIC CATALYST ON THE DEGRADATIVE OLIGOMERIZATION OF THYMIDINE 5'-p-NITROPHENYLPHOSPHATE
Shimidzu, Takeo,Murakami, Akira
, p. 51 - 54 (2007/10/02)
Degradative oligomerization of thymidine 5'-p-nitrophenylphosphate(PNP-pT) were studied in the presence of imidazole, its derivatives, and metal ions.PNP-pT was degraded to give several kinds of thymidylic acid oligomers such as pTpT, TppT, cyclic-pTpT.The linearities of the structures of the obtained oligomers depended on the linearities of the structures of imidazole derivatives.Metal ions favoured formation of the cyclic dimer.
