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Novel RNA base pair with higher specificity using single selenium atom.

Sun H, Sheng J, Hassan AE, Jiang S, Gan J, Huang Z - Nucleic Acids Res. (2012)

Bottom Line: Specificity of nucleobase pairing provides essential foundation for genetic information storage, replication, transcription and translation in all living organisms.In order to increase U/A pairing specificity, we have hypothesized to discriminate against U/G wobble pair by tailoring the steric and electronic effects at the 2-exo position of uridine and replacing the 2-exo oxygen with a selenium atom.We reveal that the (Se)U/A pair maintains a structure virtually identical to the native U/A base pair, while discriminating against U/G wobble pair.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Georgia State University, Atlanta, Georgia 30303, USA.

ABSTRACT
Specificity of nucleobase pairing provides essential foundation for genetic information storage, replication, transcription and translation in all living organisms. However, the wobble base pairs, where U in RNA (or T in DNA) pairs with G instead of A, might compromise the high specificity of the base pairing. The U/G wobble pairing is ubiquitous in RNA, especially in non-coding RNA. In order to increase U/A pairing specificity, we have hypothesized to discriminate against U/G wobble pair by tailoring the steric and electronic effects at the 2-exo position of uridine and replacing the 2-exo oxygen with a selenium atom. We report here the first synthesis of the 2-Se-U-RNAs as well as the 2-Se-uridine ((Se)U) phosphoramidite. Our biophysical and structural studies of the (Se)U-RNAs indicate that this single atom replacement can indeed create a novel U/A base pair with higher specificity than the natural one. We reveal that the (Se)U/A pair maintains a structure virtually identical to the native U/A base pair, while discriminating against U/G wobble pair. This oxygen replacement with selenium offers a unique chemical strategy to enhance the base pairing specificity at the atomic level.

Show MeSH
Synthesis of SeU-phosphoramidite 11 and RNAs (12). Reagents and conditions: (a) CH3I, DBU, DMF; (b) Se, NaBH4, EtOH; (c) TBDMS-Cl, imidazole, DMF; (d) ICH2CH2CN, (i-Pr)2NEt, CH2Cl2; (e) (i-Pr2N)2P(Cl)OCH2CH2CN, (i-Pr)2NEt, CH2Cl2; (f) solid-phase synthesis.
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gks010-SCH1: Synthesis of SeU-phosphoramidite 11 and RNAs (12). Reagents and conditions: (a) CH3I, DBU, DMF; (b) Se, NaBH4, EtOH; (c) TBDMS-Cl, imidazole, DMF; (d) ICH2CH2CN, (i-Pr)2NEt, CH2Cl2; (e) (i-Pr2N)2P(Cl)OCH2CH2CN, (i-Pr)2NEt, CH2Cl2; (f) solid-phase synthesis.


Novel RNA base pair with higher specificity using single selenium atom.

Sun H, Sheng J, Hassan AE, Jiang S, Gan J, Huang Z - Nucleic Acids Res. (2012)

Synthesis of SeU-phosphoramidite 11 and RNAs (12). Reagents and conditions: (a) CH3I, DBU, DMF; (b) Se, NaBH4, EtOH; (c) TBDMS-Cl, imidazole, DMF; (d) ICH2CH2CN, (i-Pr)2NEt, CH2Cl2; (e) (i-Pr2N)2P(Cl)OCH2CH2CN, (i-Pr)2NEt, CH2Cl2; (f) solid-phase synthesis.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3367167&req=5

gks010-SCH1: Synthesis of SeU-phosphoramidite 11 and RNAs (12). Reagents and conditions: (a) CH3I, DBU, DMF; (b) Se, NaBH4, EtOH; (c) TBDMS-Cl, imidazole, DMF; (d) ICH2CH2CN, (i-Pr)2NEt, CH2Cl2; (e) (i-Pr2N)2P(Cl)OCH2CH2CN, (i-Pr)2NEt, CH2Cl2; (f) solid-phase synthesis.
Bottom Line: Specificity of nucleobase pairing provides essential foundation for genetic information storage, replication, transcription and translation in all living organisms.In order to increase U/A pairing specificity, we have hypothesized to discriminate against U/G wobble pair by tailoring the steric and electronic effects at the 2-exo position of uridine and replacing the 2-exo oxygen with a selenium atom.We reveal that the (Se)U/A pair maintains a structure virtually identical to the native U/A base pair, while discriminating against U/G wobble pair.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Georgia State University, Atlanta, Georgia 30303, USA.

ABSTRACT
Specificity of nucleobase pairing provides essential foundation for genetic information storage, replication, transcription and translation in all living organisms. However, the wobble base pairs, where U in RNA (or T in DNA) pairs with G instead of A, might compromise the high specificity of the base pairing. The U/G wobble pairing is ubiquitous in RNA, especially in non-coding RNA. In order to increase U/A pairing specificity, we have hypothesized to discriminate against U/G wobble pair by tailoring the steric and electronic effects at the 2-exo position of uridine and replacing the 2-exo oxygen with a selenium atom. We report here the first synthesis of the 2-Se-U-RNAs as well as the 2-Se-uridine ((Se)U) phosphoramidite. Our biophysical and structural studies of the (Se)U-RNAs indicate that this single atom replacement can indeed create a novel U/A base pair with higher specificity than the natural one. We reveal that the (Se)U/A pair maintains a structure virtually identical to the native U/A base pair, while discriminating against U/G wobble pair. This oxygen replacement with selenium offers a unique chemical strategy to enhance the base pairing specificity at the atomic level.

Show MeSH