scholarly journals Sequence-specific artificial ribonucleases. I. Bis-imidazole-containing oligonucleotide conjugates prepared using precursor-based strategy

2004 ◽  
Vol 32 (13) ◽  
pp. 3887-3897 ◽  
Author(s):  
N. G. Beloglazova
2008 ◽  
Vol 52 (1) ◽  
pp. 529-530
Author(s):  
I. Serpokrylova ◽  
L. Koroleva ◽  
N. Svischeva ◽  
D. Novopashina ◽  
V. Silnikov

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Natalia G. Beloglazova ◽  
Martin M. Fabani ◽  
Nikolai N. Polushin ◽  
Vladimir V. Sil'nikov ◽  
Valentin V. Vlassov ◽  
...  

Design of site-selective artificial ribonucleases (aRNases) is one of the most challenging tasks in RNA targeting. Here, we designed and studied oligonucleotide-based aRNases containingmultipleimidazole residues in the catalytic part and systematically varied structure of cleaving constructs. We demonstrated that the ribonuclease activity of the conjugates is strongly affected by the number of imidazole residues in the catalytic part, the length of a linker between the catalytic imidazole groups of the construct and the oligonucleotide, and the type of anchor group, connecting linker structure and the oligonucleotide. Molecular modeling of the most active aRNases showed that preferable orientation(s) of cleaving constructs strongly depend on the structure of the anchor group and length of the linker. The inclusion of deoxyribothymidine anchor group significantly reduced the probability of cleaving groups to locate near the cleavage site, presumably due to a stacking interaction with the neighbouring nucleotide residue. Altogether the obtained results show that dynamics factors play an important role in site-specific RNA cleavage. Remarkably high cleavage activity was displayed by the conjugates with the most flexible and extended cleaving construct, which presumably provides a better opportunity for imidazole residues to be correctly positioned in the vicinity of scissile phosphodiester bond.


2021 ◽  
Vol 11 (3) ◽  
pp. 1174
Author(s):  
Alina Derzhalova ◽  
Oleg Markov ◽  
Alesya Fokina ◽  
Yasuo Shiohama ◽  
Timofei Zatsepin ◽  
...  

New lipid conjugates of DNA and RNA incorporating one to four [(4-dodecylphenyl)sulfonyl]phosphoramidate or (hexadecylsulfonyl)phosphoramidate groups at internucleotidic positions near the 3′ or 5′-end were synthesized and characterized. Low cytotoxicity of the conjugates and their ability to be taken up into cells without transfection agents were demonstrated. Lipid-conjugated siRNAs targeting repulsive guidance molecules a (RGMa) have shown a comparable gene silencing activity in PK-59 cells to unmodified control siRNA when delivered into the cells via Lipofectamine mediated transfection.


2018 ◽  
Vol 13 ◽  
pp. 483-492 ◽  
Author(s):  
Marc Nothisen ◽  
Phanélie Perche-Létuvée ◽  
Jean-Paul Behr ◽  
Jean-Serge Remy ◽  
Mitsuharu Kotera

2001 ◽  
Vol 1 (1) ◽  
pp. 217-218 ◽  
Author(s):  
K. Obara ◽  
T. Ishihara ◽  
T. Akaike ◽  
A. Maruyama

2001 ◽  
Vol 20 (4-7) ◽  
pp. 1259-1262 ◽  
Author(s):  
V. V. Koval ◽  
A. A. Chernonosov ◽  
T. V. Abramova ◽  
T. M. Ivanova ◽  
O. S. Fedorova ◽  
...  

2020 ◽  
Vol 6 (15) ◽  
pp. eaaz0051 ◽  
Author(s):  
Xinyu Ling ◽  
Bingteng Xie ◽  
Xiaoqin Gao ◽  
Liying Chang ◽  
Wei Zheng ◽  
...  

Site-specific chemical conjugation of proteins can enhance their therapeutic and diagnostic utility but has seldom been applied to CRISPR-Cas9, which is a rapidly growing field with great therapeutic potential. The low efficiency of homology-directed repair remains a major hurdle in CRISPR-Cas9–mediated precise genome editing, which is limited by low concentration of donor DNA template at the cleavage site. In this study, we have developed methodology to site-specifically conjugate oligonucleotides to recombinant Cas9 protein containing a genetically encoded noncanonical amino acid with orthogonal chemical reactivity. The Cas9-oligonucleotide conjugates recruited an unmodified donor DNA template to the target site through base pairing, markedly increasing homology-directed repair efficiency in both human cell culture and mouse zygotes. These chemically modified Cas9 mutants provide an additional tool, one that is complementary to chemically modified nucleic acids, for improving the utility of CRISPR-Cas9–based genome-editing systems.


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