3590-47-4Relevant articles and documents
OLIGONUCLEOTIDE HAVING NON-NATURAL NUCLEOTIDE AT 5'-TERMINAL THEREOF
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Paragraph 0645-0648; 0666; 0667; 0668; 1094-1095, (2018/01/19)
An oligonucleotide having a nucleotide residue or a nucleoside residue represented by formula (I) {wherein X1 is an oxygen atom or the like, R1 is formula (IIA) (wherein R5A is halogen or the like, and R6A is a hydrogen atom or the like), formula (IVA) (wherein Y3A is a nitrogen atom or the like, and Y4A is CH or the like), or the like, R2 is a hydrogen atom, hydroxy, halogen, or optionally substituted lower alkoxy, and R3 is a hydrogen atom or the like, or formula (VI) (wherein n2 is 1, 2 or 3)} at the 5′ end thereof, wherein the nucleotide residue or the nucleoside residue binds to an adjacent nucleotide residue through the oxygen atom at position 3, is provided.
Fully automated continuous meso-flow synthesis of 5′-nucleotides and deoxynucleotides
Zhu, Chenjie,Tang, Chenglun,Cao, Zhi,He, Wei,Chen, Yong,Chen, Xiaochun,Guo, Kai,Ying, Hanjie
, p. 1575 - 1581 (2015/02/19)
The first continuous meso-flow synthesis of natural and non-natural 5′-nucleotides and deoxynucleotides is described, representing a significant advance over the corresponding in-flask method. By means of this meso-flow technique, a synthesis with time consumption and high-energy consumption becomes facile to generate products with great efficiency. An abbreviated duration, satisfactory output, and mild reaction conditions are expected to be realized under the present procedure.
5-Substituted UTP derivatives as P2Y2 receptor agonists
Knoblauch, Bernd H.A.,Mueller, Christa E.,Jaerlebark, Leif,Lawoko, Grace,Kottke, Thomas,Wikstroem, Martin A.,Heilbronn, Edith
, p. 809 - 824 (2007/10/03)
A series of 5-alkyl-substituted UTP derivatives, which had been synthesized previously with a moderate degree of purity, was resynthesized, purified, and characterized. Synthetic and purification procedures were optimized. New spectroscopic data, including 13C- and 31P NMR data, are presented. Phosphorylation reactions yielded a number of side products, such as the 2'-, 3'-, and 5'-monophosphates, the 2',3'-cyclic monophosphates, and the 2',3'-cyclic phosphates of the 5'-triphosphates. Furthermore, raw products were contaminated with inorganic phosphates, including cyclometatriphosphate, phosphate, and pyrophosphate. The uracil nucleotides were investigated for their potency to increase intracellular calcium concentrations by stimulation of P2Y2 receptors (P2Y2R) on NG108- 15 cells, a mouse neuroblastoma x glioma cell line, and in human basal epithelial airway cells, including a cystic fibrosis (CF/T43) cell line. UTP exhibited EC50 values of ca. 1 μM (in NG108-15 cells) and of 0.1 μM (in CF/T43 cells), respectively. 5-Substituted UTP derivatives were agonists at the P2Y2R, but were less potent than UTP. 5-Ethyl-UTP, for example, exhibited an EC50 value of 99 μM at P2Y2R of NG108-15 cells and proved to be a full agonist. With increasing volume of the 5- substituent of UTP derivatives, P2Y2 activity decreased.
One-electron-reduction potentials of pyrimidine bases, nucleosides, and nucleotides in aqueous solution. Consequences for DNA redox chemistry
Steenken,Telo,Novais,Candeias
, p. 4701 - 4709 (2007/10/02)
The reduction potentials in aqueous solution of the pyrimidine bases, nucleosides, and nucleotides of uracil (U) and thymine (T) were determined using the technique of pulse radiolysis with time-resolved spectrophotometric detection. The electron adducts of U and T were found to undergo reversible electron exchange with a series of ring-substituted N-methylpyridinium cations with known reduction potential. From the concentrations of the pyrimidine electron adducts and the reduced N-methylpyridinium compounds at electron-transfer equilibrium, the thermodynamical equilibrium constants were obtained and from these the reduction potentials. The results show U and T and their nucleosides and nucleotides to have very similar reduction potentials, ～ -1.1 V/NHE at pH 8, i.e., the effect of methylation at C5, C6, or of substitution at N1 is small, ≤0.1 V. In the case of cytosine (C) the electron adduct is protonated (probably at N3), even up to pH 13. The protonated adduct (C(H)?) undergoes a reversible electron transfer with the N-methylpyridinium cations. This is accompanied in one direction by transfer of a proton but by that of a water molecule in the other direction. As a result of the protonation of the electron adduct, the effective ease of reduction of C in aqueous solution is similar to that of U and T. It is suggested that in DNA the tendency for C?- to be protonated (by its complementary base G) is larger by ≥10 orders of magnitude than that for protonation of T?- by its complementary base A. This results in C and not T being the most easily reduced base in DNA. A further consequence is that lack of neutralization by intrapair proton transfer of T?- enables the irreversible extra-pair protonation on C6 of the radical anion to take place.
