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Cyano Modification on Uridine Decreases Base-Pairing Stability and Specificity through Neighboring Disruption in RNA Duplex.
Mao, Song; Ranganathan, Srivathsan V; Tsai, Hsu-Chun; Haruehanroengra, Phensinee; Shen, Fusheng; Valsangkar, Vibhav A; Han, Bo; Hassan, Abdalla E A; Chen, Alan; Sheng, Jia.
Affiliation
  • Mao S; Department of Chemistry and The RNA Institute, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY, 12222, USA.
  • Ranganathan SV; Department of Chemistry and The RNA Institute, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY, 12222, USA.
  • Tsai HC; Department of Chemistry and The RNA Institute, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY, 12222, USA.
  • Haruehanroengra P; Department of Chemistry and The RNA Institute, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY, 12222, USA.
  • Shen F; Department of Chemistry and The RNA Institute, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY, 12222, USA.
  • Valsangkar VA; Department of Chemistry and The RNA Institute, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY, 12222, USA.
  • Han B; Department of Chemistry and The RNA Institute, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY, 12222, USA.
  • Hassan AEA; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
  • Chen A; Applied Nucleic Acids Research Center, Faculty of Science, Zagazig University, Zagazig, Egypt.
  • Sheng J; Department of Chemistry and The RNA Institute, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY, 12222, USA.
Chembiochem ; 19(24): 2558-2565, 2018 12 18.
Article in En | MEDLINE | ID: mdl-30294879
ABSTRACT
5-Cyanomethyluridine (cnm5 U) and 5-cyanouridine (cn5 U), the two uridine analogues, were synthesized and incorporated into RNA oligonucleotides. Base-pairing stability and specificity studies in RNA duplexes indicated that cnm5 U slightly decreased the stability of the duplex but retained the base-pairing preference. In contrast, cn5 U dramatically decreased both base-pairing stability and specificity between UA and other noncanonical UG, UU, and UC pairs. In addition, the cn5 UG pair was found to be stronger than the cn5 UA pair and the other mismatched pairs in the context of a RNA duplex; this implied that cn5 U might slightly prefer to recognize G over A. Our mechanistic studies by molecular simulations showed that the cn5 U modification did not directly affect the base pairing of the parent nucleotide; instead, it weakened the neighboring base pair in the 5' side of the modification in the RNA duplexes. Consistent with the simulation data, replacing the Watson-Crick AU pair to a mismatched CU pair in the 5'-neighboring site did not affect the overall stability of the duplex. Our work reveals the significance of the electron-withdrawing cyano group in natural tRNA systems and provides two novel building blocks for constructing RNA-based therapeutics.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Uridine / RNA / Base Pairing / RNA Stability / Nitriles Language: En Journal: Chembiochem Journal subject: BIOQUIMICA Year: 2018 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Uridine / RNA / Base Pairing / RNA Stability / Nitriles Language: En Journal: Chembiochem Journal subject: BIOQUIMICA Year: 2018 Type: Article Affiliation country: United States