Synthesis and Properties of Nucleic Acid Analogues Consisting of a Benzene—Phosphate Backbone.

Ueno, Yoshihito; Kato, Takumi; Sato, Kumiko; Ito, Yosoji; Yoshida, Mahito; Inoue, T.; Shibata, Aya; Ebihara, Masahiro; Kitade, Yukio

doi:10.1002/chin.200552187

Cited by 3 publications

(4 citation statements)

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“…[17][18][19] Therefore, we consider that BP at the 3 0 -overhang region may be associated with the PAZ domain of Ago2. 13,14 These findings were reflected by the evidence that the protein level of ERK5, one of the major targets of miR-143, was downregulated in accordance with the activities of the various synthetic miR-143s with modified passenger sequences. Furthermore, the isolation of miRNA by using anti-Ago2 antibody indicated a higher level of miR-143BP/3 0 -2 M in Ago2-binding miRNAs than that of miR-143BP/4 M, which probably caused the more potent suppression of ERK5 expression.…”

Section: Discussionmentioning

confidence: 88%

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Role of anti-oncomirs miR-143 and -145 in human colorectal tumors

et al. 2010

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We examined the expression levels of microRNAs (miRNAs (miRs)) in colorectal tumors (63 cancer specimens and 65 adenoma specimens) and paired non-tumorous tissues. Decreased expression of miR-143 and -145 was frequently observed in the adenomas and cancers tested, compared with miR-34a downregulation and miR-21 upregulation. Expression profiles of miR-143 and -145 were not associated with any clinical features. As the downregulation of miR-143 and -145 was observed even in the early phase of adenoma formation, the decreased expression of both miRs would appear to contribute mainly to the initiation step of tumorigenesis, not to the progression stage, and not to clinical prognostic factors. For clinical application, we changed the sequences of the passenger strand in the miR-143 duplex and performed chemical modification at the 3 0 -overhang portion of miR-143, leading to greater activity and stability to nuclease. The cell growth inhibitory effect of the chemically modified synthetic miR-143 in vitro was greater than that of endogenous miR-143. The miR-143 showed a significant tumor-suppressive effect on xenografted tumors of DLD-1 human colorectal cancer cells. These findings suggest that miR-143 and -145 are important oncorelated genes for the initiation step of colorectal tumor development and that the chemically modified synthetic miR-143 may be a hopeful candidate as an RNA medicine for the treatment of colorectal tumors.

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Section: Discussionmentioning

confidence: 88%

“…13,14 Deprotection of bases and phosphates was performed in concentrated NH 4 OH/EtOH (3:1, v/v) at room temperature for 12 h. The 2 0 -tert-butyldimethylsilyl groups were removed by treatment for 12 h with 1.0 M tetrabutylammonium fluoride in tetrahydrofuran at room temperature.…”

Section: Modification For Higher Nuclease-resistance Property Of Mirnmentioning

confidence: 99%

Role of anti-oncomirs miR-143 and -145 in human colorectal tumors

et al. 2010

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“…Our recent work has revealed that changing the structure of the passenger strand of the miR-143 duplex enhanced the growth inhibition of human colon cancer DLD-1 cells and that chemical modification of the 3′-overhang of miR-143 using aromatic moieties, such as benzene(B)-pyridine(P) analogs (BP-type), improved its resistance against nucleases (13,14). The administration of such chemically modified miR-143BPs via intravenous injection resulted in a potent tumor-suppressive effect on xenografted human colon cancer cells.…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs and Their Therapeutic Potential for Human Diseases: MicroRNAs, miR-143 and -145, Function as Anti-oncomirs and the Application of Chemically Modified miR-143 as an Anti-cancer Drug

Kitade

Akao

2010

J Pharmacol Sci

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Abstract.We examined the expression levels of microRNAs (miRNAs; miRs) in colorectal tumors (63 cancer specimens and 65 adenoma specimens) compared to adjacent non-tumorous tissues. Decreased expression of miR-143 and -145 was frequently observed in the adenoma and cancer samples. As the down-regulation of miR-143 and -145 was observed even in the early phase of adenoma formation, their decreased expression would appear to contribute mainly to the initiation of tumorigenesis. For clinical application, we added aromatic benzene-pyridine (BP-type) analogs to the 3′-overhang region of the RNA-strand and changed the sequences of the passenger strand in the miR-143 duplex (miR-143BPs), leading to greater activity and increased resistance to nuclease. The cell growth inhibitory effect of the chemically modified miR-143BPx in vitro was greater than that of the endogenous miR-143. The modified miR-143BPx showed a significant tumor-suppressive effect on xenografted tumors of human colorectal cancer DLD-1 cells. These findings suggest that miR-143 and -145 are important onco-related genes for the initiation of colorectal tumor development and that chemically modified miR-143BPx may be a candidate for an RNA medicine for the treatment of colorectal tumors.

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“…Previously, authors reported the synthesis and properties of oligonucleotide analogs containing benzene‐phosphate backbone which is highly resistant to nuclease activity (Ueno et al., , ). However, the oligonucleotides were unable to form stable duplexes with complementary RNA and DNA.…”

Section: Commentarymentioning

confidence: 99%

Synthesis of the Phosphoramidite Units for Benzene‐Glycol Nucleic Acid

Maeda

Niwa

Ueno

2017

CP Nucleic Acid Chemistry

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Benzene-glycol nucleic acid-DNA chimeras form thermally and thermodynamically stable duplexes with complementary RNAs, and have base-discriminating abilities. This unit describes the synthesis of four nucleoside analogs, an adenine, cytosine, thymine, and guanine analogs with base-benzene-glycol structure. The synthesis starts with conversion of (S)-mandelic acid in arylboronic acid derivative, common intermediate. Nucleobase coupling of the intermediate and phosphitylation afford to phosphoroamidite units. © 2017 by John Wiley & Sons, Inc.

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Synthesis and Properties of Nucleic Acid Analogues Consisting of a Benzene—Phosphate Backbone.

Cited by 3 publications

References 1 publication

Role of anti-oncomirs miR-143 and -145 in human colorectal tumors

Role of anti-oncomirs miR-143 and -145 in human colorectal tumors

MicroRNAs and Their Therapeutic Potential for Human Diseases: MicroRNAs, miR-143 and -145, Function as Anti-oncomirs and the Application of Chemically Modified miR-143 as an Anti-cancer Drug

Synthesis of the Phosphoramidite Units for Benzene‐Glycol Nucleic Acid

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