Universal bases: Base pairing and duplex stability of oligonucleotides containing pyrrolo[2,3-d]pyrimidines and 5-nitroindole nucleosides

2005 ◽  
Author(s):  
Peter Leonard ◽  
Xin Ming ◽  
Anup M. Jawalekar ◽  
Wilma Thür ◽  
Dieter Heindl ◽  
...  
Keyword(s):  
Base Pairing ◽  
Duplex Stability ◽  
Universal Bases

Effect of a Hydrogen Bonding Carboxamide Group on Universal Bases

2006 ◽  
Vol 71 (6) ◽  
pp. 899-911 ◽  
Author(s):  
Kathleen Too ◽  
Daniel M. Brown ◽  
Philipp Holliger ◽  
David Loakes
Keyword(s):  
Hydrogen Bonding ◽  
Nitro Group ◽  
Pyrrole Ring ◽  
Major Groove ◽  
Duplex Stability ◽  
Universal Bases

A number of aromatic universal base analogues have been described in the literature, but most are non-hydrogen bonding. We have examined the effect of introducing hydrogen bonding carboxamide groups onto the pyrrole ring of 5-nitroindole. The modified analogues retain universal base features, but there are no overall effects on duplex stability. This leads to the suggestion that the nitro group is within the hydrogen bonding face of the duplex, and the hydrogen bonding carboxamide group is in the duplex major groove.

Intrastrand locks increase duplex stability and base pairing selectivity

2011 ◽  
Vol 47 (38) ◽  
pp. 10824 ◽  
Author(s):  
Cora Prestinari ◽  
Clemens Richert
Keyword(s):  
Base Pairing ◽  
Duplex Stability

scholarly journals Base pairing, structural and functional insights into N4-methylcytidine (m4C) and N4,N4-dimethylcytidine (m42C) modified RNA

2020 ◽  
Vol 48 (18) ◽  
pp. 10087-10100
Author(s):  
Song Mao ◽  
Bartosz Sekula ◽  
Milosz Ruszkowski ◽  
Srivathsan V Ranganathan ◽  
Phensinee Haruehanroengra ◽  
...  
Keyword(s):  
Base Pairing ◽  
Reverse Transcriptases ◽  
X Ray Crystallography ◽  
Coding Efficiency ◽  
Gene Replication ◽  
Nucleotide Incorporation ◽  
Duplex Stability ◽  
Rna Duplexes ◽  
Fine Tune ◽  
Hiv 1

Abstract The N4-methylation of cytidine (m4C and m42C) in RNA plays important roles in both bacterial and eukaryotic cells. In this work, we synthesized a series of m4C and m42C modified RNA oligonucleotides, conducted their base pairing and bioactivity studies, and solved three new crystal structures of the RNA duplexes containing these two modifications. Our thermostability and X-ray crystallography studies, together with the molecular dynamic simulation studies, demonstrated that m4C retains a regular C:G base pairing pattern in RNA duplex and has a relatively small effect on its base pairing stability and specificity. By contrast, the m42C modification disrupts the C:G pair and significantly decreases the duplex stability through a conformational shift of native Watson-Crick pair to a wobble-like pattern with the formation of two hydrogen bonds. This double-methylated m42C also results in the loss of base pairing discrimination between C:G and other mismatched pairs like C:A, C:T and C:C. The biochemical investigation of these two modified residues in the reverse transcription model shows that both mono- or di-methylated cytosine bases could specify the C:T pair and induce the G to T mutation using HIV-1 RT. In the presence of other reverse transcriptases with higher fidelity like AMV-RT, the methylation could either retain the normal nucleotide incorporation or completely inhibit the DNA synthesis. These results indicate the methylation at N4-position of cytidine is a molecular mechanism to fine tune base pairing specificity and affect the coding efficiency and fidelity during gene replication.

Molecular Dynamics Study of DNA Duplex Containing Carbazole-Derived Universal Base

2012 ◽  
Vol 506 ◽  
pp. 258-261
Author(s):  
W. Soodsawang ◽  
T. Benchawan ◽  
U. Wichai ◽  
Y. Tantirungrotechai
Keyword(s):  
Molecular Dynamics ◽  
Md Simulations ◽  
Reference Sequence ◽  
Dna Duplexes ◽  
Structure And Dynamics ◽  
Duplex Stability ◽  
Stability Order ◽  
The Stability ◽  
Duplex Formation ◽  
Universal Bases

Universal base is a man-made residue that can be incorporated into the DNA double strands without any discrimination against natural bases (A, C, G, T). The MD simulations with AMBER99 force field were employed to investigate the structure and dynamics of the modified 15-mer DNA duplexes containing carbazole-derived universal bases: carbazole (CBZ), 3,6-dicyanocarbazole (DCC), 3,6-dinitrocarbazole (DNC), and 3-nitro-6-cyanocarbazole (NCC), where X = CBZ, DCC, DNC, or NCC, respectively. The RMSD and B-factor of the modified DNAs backbones around the universal base unit fluctuate more than the reference sequence in the same position. The thermodynamic parameter for duplex stability was estimated by using MM-PBSA method. The averaged duplex formation free energy (ΔG) of all modified DNAs exhibited that the stability order was approximately DNC>NCC>CBZ>DCC, which differed from the reference sequence exceptional DNC unit. The averaged ΔG value of the DNC unit is very close to that of the reference sequence. This calculation indicated that the DNC unit can be considered as a good candidate for using as a universal base.

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