期刊
CHEMISTRY-A EUROPEAN JOURNAL
卷 19, 期 25, 页码 8163-8181出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.201203330
关键词
acidity; basicity; DNA; metal ions; RNA; tautomerism
资金
- Swiss National Science Foundation
- European Research Council (ERC Starting Grant)
- University of Zurich
- University of Granada
- University of Basel
- Polish Academy of Sciences
- Lodz University of Technology
- Ministerio de Educacion, Cultura y Deporte, Spain (FPU Program)
- Marie Heim-Vogtlin fellowship
The intrinsic acid-base properties of the hexa-2-deoxynucleoside pentaphosphate, d(ApGpGpCpCpT) [=(A1G2G3C4C5T6)=(HNPP)5-] have been determined by 1HNMR shift experiments. The pKa values of the individual sites of the adenosine (A), guanosine (G), cytidine (C), and thymidine (T) residues were measured in water under single-strand conditions (i.e., 10% D2O, 47 degrees C, I=0.1M, NaClO4). These results quantify the release of H+ from the two (N7)H+ (GG), the two (N3)H+ (CC), and the (N1)H+ (A) units, as well as from the two (N1)H (GG) and the (N3)H (T) sites. Based on measurements with 2-deoxynucleosides at 25 degrees C and 47 degrees C, they were transferred to pKa values valid in water at 25 degrees C and I=0.1M. Intramolecular stacks between the nucleobases A1 and G2 as well as most likely also between G2 and G3 are formed. For HNPP three pKa clusters occur, that is those encompassing the pKa values of 2.44, 2.97, and 3.71 of G2(N7)H+, G3(N7)H+, and A1(N1)H+, respectively, with overlapping buffer regions. The tautomer populations were estimated, giving for the release of a single proton from five-fold protonated H5(HNPP)+/-, the tautomers (G2)N7, (G3)N7, and (A1)N1 with formation degrees of about 74, 22, and 4%, respectively. Tautomer distributions reveal pathways for proton-donating as well as for proton-accepting reactions both being expected to be fast and to occur practically at no cost. The eight pKa values for H5(HNPP)+/- are compared with data for nucleosides and nucleotides, revealing that the nucleoside residues are in part affected very differently by their neighbors. In addition, the intrinsic acidity constants for the RNA derivative r(A1G2G3 C4C5U6), where U=uridine, were calculated. Finally, the effect of metal ions on the pKa values of nucleobase sites is briefly discussed because in this way deprotonation reactions can easily be shifted to the physiological pH range.
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