Synthesis and properties of GuNA purine/pyrimidine nucleosides and oligonucleotides

2020 ◽  
Vol 18 (46) ◽  
pp. 9461-9472
Author(s):  
Shinji Kumagai ◽  
Hiroaki Sawamoto ◽  
Tomo Takegawa-Araki ◽  
Yuuki Arai ◽  
Shuhei Yamakoshi ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Modified Oligonucleotides ◽  
Robust Method ◽  
Facile Synthesis ◽  
Pyrimidine Nucleosides ◽  
Thymine Adenine ◽  
Purine Pyrimidine

Facile synthesis of GuNA (guanidine-bridged nucleic acid) phosphoramidites bearing thymine, adenine, guanine, and 5-methylcytosine nucleobases and a robust method for the preparation of GuNA-modified oligonucleotides are described.

scholarly journals Facile synthesis and fundamental properties of an N-methylguanidine-bridged nucleic acid (GuNA[NMe])

2018 ◽  
Vol 16 (35) ◽  
pp. 6531-6536 ◽  
Author(s):  
Naohiro Horie ◽  
Shinji Kumagai ◽  
Yutaro Kotobuki ◽  
Takao Yamaguchi ◽  
Satoshi Obika
Keyword(s):  
Nucleic Acid ◽  
Modified Oligonucleotides ◽  
Facile Synthesis ◽  
Single Stranded Dna ◽  
Enzymatic Stability ◽  
Fundamental Properties ◽  
Dna And Rna

The GuNA[NMe]-modified oligonucleotides exhibited excellent duplex-forming ability towards the complementary single-stranded DNA and RNA, and showed robust enzymatic stability.

scholarly journals Synthesis and properties of oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing adenine, guanine, or 5-methylcytosine nucleobases

2021 ◽  
Vol 17 ◽  
pp. 622-629
Author(s):  
Naohiro Horie ◽  
Takao Yamaguchi ◽  
Shinji Kumagai ◽  
Satoshi Obika
Keyword(s):  
Nucleic Acid ◽  
Binding Affinity ◽  
Antisense Oligonucleotides ◽  
Modified Oligonucleotides ◽  
Biophysical Properties ◽  
Chemical Modifications ◽  
Antisense Technology ◽  
Strong Affinity ◽  
The Stability

Chemical modifications have been extensively used for therapeutic oligonucleotides because they strongly enhance the stability against nucleases, binding affinity to the targets, and efficacy. We previously reported that oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing the thymine (T) nucleobase show excellent biophysical properties for applications in antisense technology. In this paper, we describe the synthesis of GuNA[Me] phosphoramidites bearing other typical nucleobases including adenine (A), guanine (G), and 5-methylcytosine (mC). The phosphoramidites were successfully incorporated into oligonucleotides following the method previously developed for the GuNA[Me]-T-modified oligonucleotides. The binding affinity of the oligonucleotides modified with GuNA[Me]-A, -G, or -mC toward the complementary single-stranded DNAs or RNAs was systematically evaluated. All of the GuNA[Me]-modified oligonucleotides were found to have a strong affinity for RNAs. These data indicate that GuNA[Me] could be a useful modification for therapeutic antisense oligonucleotides.

scholarly journals The degradation of nucleic acids in, and the removal of breakdown products from the small intestines of steers

1980 ◽  
Vol 44 (1) ◽  
pp. 99-112 ◽  
Author(s):  
A. B. McAllan
Keyword(s):  
Uric Acid ◽  
Small Intestine ◽  
Polyethylene Glycol ◽  
Nucleic Acid ◽  
Nucleic Acids ◽  
Terminal Ileum ◽  
Pyrimidine Nucleosides ◽  
Small Intestines ◽  
Rna And Dna ◽  
Serum And Urine

1. Nucleic acids and breakdown products were estimated in digesta taken from different sites in the small intestines of slaughtered steers given different diets. Amounts passing different sites were compared using cellulose as a non-digestible marker. The validity of this marker was checked with chromic oxide in some experiments. In other experiments, nucleic acids or derivatives were infused into the proximal duodenum of steers receiving diets of approximately equal proportions of flaked maize and hay. The amounts disappearing during passage through the small intestine were estimated using polyethylene glycol (PEG) as a non- absorbable marker.2. In the slaughter experiments the amounts of nucleic acids entering the small intestine varied with the type of diet. RNA and DNA disappeared on average, to extents of 89% and 80% respectively between the abomasum and the terminal ileum, irrespective of the diet. RNA disappearance occurred almost entirely in the proximal quarter of the small intestine, whereas that of DNA extended further along the tract.3. Nucleic acid degradation in the upper small intestine was accompanied by the transient appearance of adenosine, guanosine and pyrimidine nucleosides. These products were in greatest concentration in digesta from the first quarter of the small intestine and had generally completely disappeared by the terminal ileum.4. Of the different substances infused into the small intestine, free nucleic acids were removed to extents greater than 97%, adenine, guanine and uracil had completely disappeared, thymine and xanthine to approximately 80% and 95% and hypoxanthine and cytosine to only 51% and 48% respectively. The nucleosides adenosine and cytidine were also completely removed in the small intestine but were replaced, in part, by the catabolic products inosine plus hypoxanthine or cytosine respectively. Other nucleosides were removed to approximately half the extent of the corresponding bases.5. Serum and urine allantoin and uric acid levels were related to the amounts of purines entering the small intestines in free or bound form.

Facile Synthesis of α-Anomeric Pyrimidine Nucleosides

1994 ◽  
Vol 13 (6-7) ◽  
pp. 1647-1654 ◽  
Author(s):  
Hiroaki Sawai ◽  
Akiko Nakamura ◽  
Hidekazu Hayashi ◽  
Kazuo Shinozuka
Keyword(s):  
Facile Synthesis ◽  
Pyrimidine Nucleosides
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