Selective Phosphonylation of 5'-Adenosine Monophosphate (5'-AMP) via Pyrophosphite [PPi(III)

Karl Kaye,Shohei Ohara,Colin W G Fishwick,Terence P Kee,Katie E R Marriott,David E Bryant

doi:10.1007/s11084-016-9497-y

Abstract

We describe here experiments which demonstrate the selective phospho-transfer from a plausibly prebiotic condensed phosphorus (P) salt, pyrophosphite [H2P2O5 2−; PPi(III)], to the phosphate group of 5′-adenosine mono phosphate (5′-AMP). We show further that this P-transfer process is accelerated both by divalent metal ions (M2+) and by organic co-factors such as acetate (AcO−). In this specific case of P-transfer from PPi(III) to 5′-AMP, we show a synergistic enhancement of transfer in the combined presence of M2+ & AcO−. Isotopic labelling studies demonstrate that hydrolysis of the phosphonylated 5′-AMP, [P(III)P(V)-5′-AMP], proceeds via nuceophilic attack of water at the Pi(III) terminus.

Highlights

Amongst the most important and ubiquitous energy-currency molecules of contemporary biochemistry are activated phosphorus (P) species, condensed polyphosphate esters such as 5′-adenosine triphosphate (5′-ATP; Fig. 1; Harold 1986)
Aqueous solutions of 5′-adenosine mono phosphate (5′-AMP) (0.1 M) at pH 7 were phosphonylated in the presence of Na2-PPi(III) (1.5 M) at ambient temperature using a procedure modified from Yamamoto (Yamamoto et al 1988) to afford a range of products, identified and quantified by 31P-NMR spectroscopy
The major product under these conditions is P-phosphonylated 5'-AMP [PPi(III-V)-5'-AMP; Fig. 2], wherein ca. 16 % of the original 5'-AMP being so phosphonylated after 1 day, rising to ca. 38 % after 6 days (Fig. 3-red control line; 2′ and 3′-functionalised products account for 2–3 % of the total)

Summary

Introduction

Amongst the most important and ubiquitous energy-currency molecules of contemporary biochemistry are activated phosphorus (P) species, condensed polyphosphate esters such as 5′-adenosine triphosphate (5′-ATP; Fig. 1; Harold 1986) These molecules can effectively drive endogonic processes when suitably coupled mechanistically (Harold 1986) subsequently. We have recently demonstrated that both Pi(III) and PPi(III) can be readily produced within hot, acidic hydrothermal environments, both lab simulations and in the field at the Hveradalur geothermal site; Kverkfjöll volcanic system, Iceland (Cousins et al 2013). Amongst such processes are the ability to promote P-transfer leading to both condensed phosphates and organophosphorus species. We ouline how divalent metal ions influence this process, in a similar manner to that observed with PPi(III-V) formation (Bryant et al 2013a, b) but how there appear to be synergistic effects in that P-transfer is accelerated when these divalent metal ions are accompanied by carboxylate-containing organic molecules

Methods

Results

Conclusion