Measurement of Nucleobase pKa Values in Model Mononucleotides Shows RNA−RNA Duplexes To Be More Stable than DNA−DNA Duplexes Export

@article{citeulike:5920565, abstract = {To understand why the RNARNA duplexes in general has a higher thermodynamic stability over the corresponding DNADNA 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 (sigma = +-0.01 to 0.02) by 1H NMR (at 500 MHz) with 2033 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 DeltapKa 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 RNARNA over the DNADNA duplexes. (4) It is also found that the relative contribution of base-pairing strength and nucleobase stacking in RNARNA over DNADNA is mutually compensating as the \% AT/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.}, author = {Acharya, P. and Cheruku, P. and Chatterjee, S. and Acharya, S. and Chattopadhyaya, J.}, citeulike-article-id = {5920565}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/ja0386546}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/ja0386546}, day = {1}, doi = {10.1021/ja0386546}, journal = {Journal of the American Chemical Society}, keywords = {dna, pka}, month = {March}, number = {9}, pages = {2862--2869}, posted-at = {2009-10-11 03:09:39}, priority = {2}, title = {Measurement of Nucleobase pKa Values in Model Mononucleotides Shows RNA−RNA Duplexes To Be More Stable than DNA−DNA Duplexes}, url = {http://dx.doi.org/10.1021/ja0386546}, volume = {126}, year = {2004} }

TY - JOUR ID - citeulike:5920565 L3 - citeulike-article-id:5920565 N2 - To understand why the RNARNA duplexes in general has a higher thermodynamic stability over the corresponding DNADNA 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 (sigma = +-0.01 to 0.02) by 1H NMR (at 500 MHz) with 2033 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 DeltapKa 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 RNARNA over the DNADNA duplexes. (4) It is also found that the relative contribution of base-pairing strength and nucleobase stacking in RNARNA over DNADNA is mutually compensating as the % AT/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. IS - 9 JF - Journal of the American Chemical Society EP - 2869 TI - Measurement of Nucleobase pKa Values in Model Mononucleotides Shows RNA−RNA Duplexes To Be More Stable than DNA−DNA Duplexes VL - 126 SP - 2862 KW - dna KW - pka AU - Acharya, P AU - Cheruku, P AU - Chatterjee, S AU - Acharya, S AU - Chattopadhyaya, J PY - 2004/03/01/ UR - http://dx.doi.org/10.1021/ja0386546 ER -