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Intrinsic Acid-Base Properties of a Hexa-2'-deoxynucleoside Pentaphosphate, d(ApGpGpCpCpT). Neighboring Effects and Isomeric Equilibria

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Domínguez-Martín Alicia, Johannsen Silke, Sigel Astrid, Operschall Bert P., Song Bin, Sigel Helmut, Okruszek Andrzej, González-Pérez Josefa María, Niclós-Gutiérrez Juan, Sigel Roland K. O.,
Project A: Photoactivated charge transfer in metal-modified nucleic acids B: NMR study on the ?-domain of the plant metallothionein Ec-1 and its cyclic analogue
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Original article (peer-reviewed)

Journal Chemistry-A European Journal
Title of proceedings Chemistry-A European Journal


The intrinsic acid-base properties of the hexa-2'-deoxynucleoside pentaphosphate, d(ApGpGpCpCpT) [= (A1•G2•G3•C4•C5•T6) = (HNPP)5–] have been determined via 1H NMR 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 (10% D2O, 47°C, I = 0.1 M, NaClO4). These results quantify the release of H+ from the two (N7)H+ (G•G), the two (N3)H+ (C•C), and the (N1)H+ (A) units, as well as from the two (N1)H (G•G) and the (N3)H (T) sites. Based on measurements with 2'-deoxynucleosides at 25° and 47°C, they were transferred to pKa values valid in water at 25°C and I = 0.1 M. 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, e.g., 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 5-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 "costs". 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(A1•G2•G3•C4•C5•U6), where U = uridine, were calculated. Finally, the effect of metal ions on the pKa values of nucleobase sites is shortly discussed because in this way deprotonation reactions can easily be shifted to the physiological pH range.