Modification of oligonucleotides with weak basic residues via the 2′-O-carbamoylethyl linker for improving nuclease resistance without loss of duplex stability and antisense activity

2019 ◽  
Vol 17 (19) ◽  
pp. 4835-4842
Author(s):  
Yoshiaki Masaki ◽  
Keishi Yamamoto ◽  
Keita Yoshida ◽  
Atsuya Maruyama ◽  
Takahito Tomori ◽  
...  

For the improvement of nuclease resistance, four kinds of new modifications through a carbamoylethyl linker were designed.

ChemBioChem ◽  
2016 ◽  
Vol 17 (21) ◽  
pp. 2054-2062 ◽  
Author(s):  
Annabelle Biscans ◽  
Jean-Rémi Bertrand ◽  
Josephine Dubois ◽  
Jacqueline Rüger ◽  
Jean-Jacques Vasseur ◽  
...  

2016 ◽  
Vol 82 (1) ◽  
pp. 12-24 ◽  
Author(s):  
Yasunori Mitsuoka ◽  
Tsuyoshi Yamamoto ◽  
Akira Kugimiya ◽  
Reiko Waki ◽  
Fumito Wada ◽  
...  

2015 ◽  
Vol 51 (19) ◽  
pp. 4024-4027 ◽  
Author(s):  
Chenguang Lou ◽  
Birte Vester ◽  
Jesper Wengel

Incorporation of a novel piperazino-modified 2′-amino-LNA monomer (PipLNA-T) into oligonucleotides leads to a pronounced affinity increase against complementary DNA and RNA and a strong stabilising effect against 3′-exonucleolytic degradation.


ChemBioChem ◽  
2012 ◽  
Vol 13 (17) ◽  
pp. 2513-2516 ◽  
Author(s):  
Aiko Yahara ◽  
Ajaya Ram Shrestha ◽  
Tsuyoshi Yamamoto ◽  
Yoshiyuki Hari ◽  
Takashi Osawa ◽  
...  

2011 ◽  
Vol 30 (7-8) ◽  
pp. 585-596 ◽  
Author(s):  
Larysa Dubey ◽  
Olga Ryazanova ◽  
Victor Zozulya ◽  
Dmytro Fedoryak ◽  
Igor Dubey

2020 ◽  
pp. 153537022097397
Author(s):  
Maria Troisi ◽  
Mitchell Klein ◽  
Andrew C Smith ◽  
Gaston Moorhead ◽  
Yonatan Kebede ◽  
...  

The objectives of this study are to evaluate the structure and protein recognition features of branched DNA four-way junctions in an effort to explore the therapeutic potential of these molecules. The classic immobile DNA 4WJ, J1, is used as a matrix to design novel intramolecular junctions including natural and phosphorothioate bonds. Here we have inserted H2-type mini-hairpins into the helical termini of the arms of J1 to generate four novel intramolecular four-way junctions. Hairpins are inserted to reduce end fraying and effectively eliminate potential nuclease binding sites. We compare the structure and protein recognition features of J1 with four intramolecular four-way junctions: i-J1, i-J1(PS1), i-J1(PS2) and i-J1(PS3). Circular dichroism studies suggest that the secondary structure of each intramolecular 4WJ is composed predominantly of B-form helices. Thermal unfolding studies indicate that intramolecular four-way junctions are significantly more stable than J1. The Tm values of the hairpin four-way junctions are 25.2° to 32.2°C higher than the control, J1. With respect to protein recognition, gel shift assays reveal that the DNA-binding proteins HMGBb1 and HMGB1 bind the hairpin four-way junctions with affinity levels similar to control, J1. To evaluate nuclease resistance, four-way junctions are incubated with DNase I, exonuclease III (Exo III) and T5 exonuclease (T5 Exo). The enzymes probe nucleic acid cleavage that occurs non-specifically (DNase I) and in a 5ʹ→3ʹ (T5 Exo) and 3ʹ→5ʹ direction (Exo III). The nuclease digestion assays clearly show that the intramolecular four-way junctions possess significantly higher nuclease resistance than the control, J1.


2002 ◽  
Vol 15 (12) ◽  
pp. 1595-1601 ◽  
Author(s):  
Victoria Valinluck ◽  
Pingfang Liu ◽  
Artur Burdzy ◽  
Junichi Ryu ◽  
Lawrence C. Sowers

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