Adenosine/guanosine-3′,5′-bis-phosphates as biocompatible and selective Zn2+-ion chelators. Characterization and comparison with adenosine/guanosine-5′-di-phosphate

Alon Haim Sayer, Eliav Blum, Dan Thomas Major, Alexandra Vardi-Kilshtain, Bosmat Levi Hevroni, Bilha Fischer

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Although involved in various physiological functions, nucleoside bis-phosphate analogues and their metal-ion complexes have been scarcely studied. Hence, here, we explored the solution conformation of 2′-deoxyadenosine- and 2′-deoxyguanosine-3′,5′-bisphosphates, 3 and 4, d(pNp), as well as their Zn2+/Mg2+ binding sites and binding-modes (i.e. inner- vs. outer-sphere coordination), acidity constants, stability constants of their Zn2+/Mg2+ complexes, and their species distribution. Analogues 3 and 4, in solution, adopted a predominant Southern ribose conformer (ca. 84%), gg conformation around C4′-C5′ and C5′-O5′ bonds, and glycosidic angle in the anti-region (213-270°). 1H- and 31P-NMR experiments indicated that Zn2+/Mg2+ ions coordinated to P5′ and P3′ groups of 3 and 4 but not to N7 nitrogen atom. Analogues 3 and 4 formed ca. 100-fold more stable complexes with Zn2+ vs. Mg2+-ions. Complexes of 3 and 4 with Mg2+ at physiological pH were formed in minute amounts (11% and 8%, respectively) vs. Zn2+ complexes (46% and 44%). Stability constants of Zn2+/Mg2+ complexes of analogues 3 and 4 (log KMLM = 4.65-4.75/2.63-2.79, respectively) were similar to those of the corresponding complexes of ADP and GDP (log KMLM = 4.72-5.10/2.95-3.16, respectively). Based on the above findings, we hypothesized that the unexpectedly low log K values of Zn2+-d(pNp) as compared to Zn2+-NDP complexes, are possibly due to formation of outer-sphere coordination in the Zn2+-d(pNp) complex vs. inner-sphere in the NDP-Zn2+ complex, in addition to loss of chelation to N7 nitrogen atom in Zn2+-d(pNp). Indeed, explicit solvent molecular dynamics simulations of 1 and 3 for 100 ns supported this hypothesis.

Original languageEnglish
Pages (from-to)7305-7317
Number of pages13
JournalDalton Transactions
Issue number16
StatePublished - 28 Apr 2015

Bibliographical note

Publisher Copyright:
© The Royal Society of Chemistry 2015.


Dive into the research topics of 'Adenosine/guanosine-3′,5′-bis-phosphates as biocompatible and selective Zn2+-ion chelators. Characterization and comparison with adenosine/guanosine-5′-di-phosphate'. Together they form a unique fingerprint.

Cite this