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Measurement of nucleobase pKa values in model mononucleotides shows RNA-RNA duplexes to be more stable than DNA-DNA duplexes

Measurement of nucleobase pKa values in model mononucleotides shows RNA-RNA duplexes to be more stable than DNA-DNA duplexes

Acharya, Parag ORCID: 0000-0003-2521-9968, Cheruku, Pradeep, Chatterjee, Subhrangshu and Chattopadhyaya, Jyoti (2004) Measurement of nucleobase pKa values in model mononucleotides shows RNA-RNA duplexes to be more stable than DNA-DNA duplexes. Journal of the American Chemical Society, 126 (9). pp. 2862-2869. ISSN 0002-7863 (Print), 1520-5126 (Online) (doi:https://doi.org/10.1021/ja0386546)

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Abstract

To understand why the RNA−RNA duplexes in general has a higher thermodynamic stability over the corresponding DNA−DNA duplexes, we have measured the pKa values of both nucleoside 3‘,5‘-bis-ethyl phosphates [Etp(d/rN)pEt] and nucleoside 3‘-ethyl phosphates [(d/rN)pEt] (N = A, G, C, or T/U), modeling as donors and acceptors of base pairs in duplexes. While the 3‘,5‘-bis-phosphates, Etp(d/rN)pEt, mimic the internucleotidic monomeric units of DNA and RNA, in which the stacking contribution is completely absent, the 3‘-ethyl phosphates, (d/rN)pEt, mimic the nucleotide at the 5‘-end. The pKa values of the nucleobase in each of these model nucleoside phosphates have been determined with low pKa error (σ = ±0.01 to 0.02) by 1H NMR (at 500 MHz) with 20−33 different pH measurements for each compound. This study has led us to show the following:  (1) All monomeric DNA nucleobases are more basic than the corresponding RNA nucleobases in their respective Etp(d/rN)pEt and (d/rN)pEt. (2) The pKa values of the monomeric nucleotide blocks as well as ΔpKa values between the donor and acceptor can be used to understand the relative base-pairing strength in the oligomeric duplexes in the RNA and DNA series. (3) The of the donor and acceptor of the base pair in duplexes enables a qualitative dissection of the relative strength of the base-pairing and stacking in the RNA−RNA over the DNA−DNA duplexes. (4) It is also found that the relative contribution of base-pairing strength and nucleobase stacking in RNA−RNA over DNA−DNA is mutually compensating as the % A−T/U content increases or decreases. This interdependency of stacking and hydrogen bonding can be potentially important in the molecular design of the base-pair mimicks to expand the alphabet of the genetic code.

Item Type: Article
Uncontrolled Keywords: free energy, nucleobases, nucleic acids, genetics, stability
Subjects: Q Science > QD Chemistry
Faculty / Department / Research Group: Faculty of Engineering & Science
Faculty of Engineering & Science > Natural Resources Institute
Faculty of Engineering & Science > Natural Resources Institute > Food & Markets Department
Last Modified: 10 Jul 2020 13:09
Selected for GREAT 2016: None
Selected for GREAT 2017: None
Selected for GREAT 2018: None
Selected for GREAT 2019: None
Selected for REF2021: None
URI: http://gala.gre.ac.uk/id/eprint/28721

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