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Department of Bioorganic Chemistry

Determination of pKa of 2'-OH in Ribonucleosides and Ribonucleotides

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2'-hydroxyl group has major structural implication in that it is involved in recognition and catalytic properties of RNA. In order to understand the specific reactivity of certain phosphate function towards stereospecific transesterification reaction, it is important to know the pKa  of 2'-OH. We have determined the experimental pKa  of 2'-OH in 18 different nucleosides and nucleotides by pH-dependent 1H NMR analyses [PDF 318, Supplementary materials]. This study has shown that different substitution of pentofuranose would make general acid-base character of 2'-OH different, which in turn may dictate its differential participation in site-specific splicing reaction.  Recently, we have measured  [PDF 342, Supporting information: parts 1, 2, 3, 4] the pKa values for internucleotidic 2'-OH of eight different diribonucleoside (3' -> 5') monophosphates under a set of uniform noninvasive conditions by 1H NMR. Thus the pKa is 12.31 (pm 0.02) for ApG and 12.41 (pm 0.04) for ApA, 12.73 (pm 0.04) for GpG and 12.71 (pm 0.08) for GpA, 12.77 (pm 0.03) for CpG and 12.88 (pm 0.02) for CpA, and 12.76 (pm 0.03) for UpG and 12.70 (pm 0.03) for UpA. By comparing the pKas of the respective 2'-OH of monomeric nucleoside 3'-ethyl phosphates with that of internucleotidic 2'-OH in corresponding diribonucleoside (3' -> 5') monophosphates, it has been confirmed that the aglycons have no significant effect on the pKa  values of their 2'-OH under our measurement condition, except for the internucleotidic 2'-OH of 9-adeninyl nucleotide at the 5'-end (ApA and ApG), which is more acidic by 0.3-0.4 pKa  units. Further work is in progress to investigate  the hydration properties of 2'-hydroxyl group in nucleos(t)ides which will have impact in understanding its reactivity. Work is also in progress to determine the pKa of 2'-OH groups in oligoribonucleotides to understand the nature of  in-line 2'-OH promoted stereospecific transesterification reactions that take place in splicing and RNA catalysis in general.

Since 2'-OH group interaction with the solvent has major structural implications in the recognition, processing, and catalytic properties of RNA, intra- and intermolecular H-bonding of 2'-OH in adenosine 3'-ethylphosphate (1), 3'-deoxyadenosine (2), and adenosine (3) as well as the nature of hydration and exchange processes of 2'-OH with water have been investigated [PDF 331].

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