Structural Basis of Duplex Thermodynamic Stability and Enhanced Nuclease Resistance of 5′-C-Methyl Pyrimidine-Modified Oligonucleotides

Three methylene-EoDNAs were synthesized from 5-methyluridine and their modified oligonucleotides showed strong binding affinity with ssRNA and high nuclease resistance.

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Synthesis and Antisense Properties of 2′β-F-Arabinouridine Modified Oligonucleotides with 4′-C-OMe Substituent

Molecules ◽

10.3390/molecules23092374 ◽

2018 ◽

Vol 23 (9) ◽

pp. 2374 ◽

Cited By ~ 2

Author(s):

Xiao-Yang He ◽

Jing Wang ◽

Dan-Dan Lu ◽

Sheng-Qi Wang

Keyword(s):

Chemical Modification ◽

Binding Affinity ◽

Therapeutic Strategy ◽

Modified Oligonucleotides ◽

Nuclease Resistance ◽

Modified Oligonucleotide

A novel 2′-F,4′-C-OMe–arabinouridine (araU) was successfully synthesized and introduced into oligonucleotides. The oligonucleotide containing 2′-F,4′-C-OMe–araU exhibited improved nuclease resistance and RNA hybridizing selective ability relative to 2′-F–araU. In particular, when 2′-F,4′-C-OMe–araU inserted into C–H⋯F–C bonding-favorable 5′–uridine–purine–3′ steps, the modified oligonucleotide showed remarkable binding affinity and selectivity to RNA complements. Thus, 2′-F,4′-C-OMe–araU has valuable antisense properties and can be used as novel chemical modification for antisense therapeutic strategy.

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ChemInform Abstract: Synthesis, Hybridization, and Nuclease Resistance Properties of 2′-O-Aminooxyethyl Modified Oligonucleotides

ChemInform ◽

10.1002/chin.199944268 ◽

2010 ◽

Vol 30 (44) ◽

pp. no-no

Author(s):

Andrew M. Kawasaki ◽

Martin D. Casper ◽

Thazha P. Prakash ◽

Sheri Manalili ◽

Henri Sasmor ◽

...

Keyword(s):

Modified Oligonucleotides ◽

Nuclease Resistance

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Sugar modified oligonucleotides: Synthesis, nuclease resistance and base pairing of oligodeoxynucleotides containing 1-(4′-thio-β-d-ribofuranosyl)-thymine

Biochemical and Biophysical Research Communications ◽

10.1016/0006-291x(92)90660-d ◽

1992 ◽

Vol 184 (2) ◽

pp. 797-803 ◽

Cited By ~ 10

Author(s):

Laurent Bellon ◽

François Morvan ◽

Jean-Louis Barascut ◽

Jean-Louis Imbach

Keyword(s):

Modified Oligonucleotides ◽

Base Pairing ◽

Nuclease Resistance ◽

Oligonucleotides Synthesis

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Structural basis of DNA synthesis opposite 8-oxoguanine by human PrimPol primase-polymerase

Nature Communications ◽

10.1038/s41467-021-24317-z ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Olga Rechkoblit ◽

Robert E. Johnson ◽

Yogesh K. Gupta ◽

Louise Prakash ◽

Satya Prakash ◽

...

Keyword(s):

Dna Synthesis ◽

Dna Polymerase ◽

Thermodynamic Stability ◽

Active Site ◽

Base Pair ◽

Translesion Synthesis ◽

Human Cells ◽

Structural Basis ◽

Human Dna ◽

Dna Template

AbstractPrimPol is a human DNA polymerase-primase that localizes to mitochondria and nucleus and bypasses the major oxidative lesion 7,8-dihydro-8-oxoguanine (oxoG) via translesion synthesis, in mostly error-free manner. We present structures of PrimPol insertion complexes with a DNA template-primer and correct dCTP or erroneous dATP opposite the lesion, as well as extension complexes with C or A as a 3′−terminal primer base. We show that during the insertion of C and extension from it, the active site is unperturbed, reflecting the readiness of PrimPol to accommodate oxoG(anti). The misinsertion of A opposite oxoG(syn) also does not alter the active site, and is likely less favorable due to lower thermodynamic stability of the oxoG(syn)•A base-pair. During the extension step, oxoG(syn) induces an opening of its base-pair with A or misalignment of the 3′-A primer terminus. Together, the structures show how PrimPol accurately synthesizes DNA opposite oxidatively damaged DNA in human cells.

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