Non-Enzymatic Oligomerization of 3’, 5’ Cyclic AMP

Abstract

Recent studies illustrate that short oligonucleotide sequences can be easily produced from nucleotide precursors in a template-free non-enzymatic way under dehydrating conditions, i.e. using essentially dry materials. Here we report that 3’,5’ cyclic AMP may also serve as a substrate of the reaction, which proceeds under moderate conditions yet with a lower efficiency than the previously reported oligomerization of 3’,5’ cyclic GMP. Optimally the oligomerization requires (i) a temperature of 80°C, (ii) a neutral to alkaline environment and (iii) a time on the order of weeks. Differences in the yield and required reaction conditions of the oligomerizations utilizing 3’,5’ cGMP and cAMP are discussed in terms of the crystal structures of the compounds. Polymerization of 3’,5’ cyclic nucleotides, whose paramount relevance in a prebiotic chemistry context has been widely accepted for decades, supports the possibility that the origin of extant genetic materials might have followed a direct uninterrupted path since its very beginning, starting from non-elaborately pre-activated monomer compounds and simple reactions.

The torpedo effect inBacillus subtilis:RNase J1 resolves stalled transcription complexes

“…Another factor whose activity significantly changed (fivefold ↑) was HelD. As reported in Costanzo et al (2016) (and references therein), the cleavage by alkali or formamide leaves the phosphate group of the attacked phosphodiester bond bound at 3 0 , initially in the 2 0 ,3 0 cyclic form (upper band in the band couples). This increased expression may help the cell to compensate for the absence of RNase J1.…”

Nonenzymatic Oligomerization of 3′,5′‐Cyclic CMP Induced by Proton and UV Irradiation Hints at a Nonfastidious Origin of RNA

“…In a more recent study, we reported that prolonged heating of dry 3′,5′‐cAMP also yields short oligonucleotide sequences . The covalent nature of the oligomerization products has been confirmed by a variety of analysis methods, such as PAGE,, MALDI‐ToF, MALDI‐ToF/ToF, NMR, and enzymatic analysis …”

“…The polymerization of 3′,5′‐cGMP at moderately high (60–80 °C) temperatures in solution (water or formamide) and under dry conditions has been described in detail . In a more recent study, we reported that prolonged heating of dry 3′,5′‐cAMP also yields short oligonucleotide sequences . The covalent nature of the oligomerization products has been confirmed by a variety of analysis methods, such as PAGE,, MALDI‐ToF, MALDI‐ToF/ToF, NMR, and enzymatic analysis …”

“…These studies were not developed further, and 3′,5′‐cyclic purine nucleotides were analyzed only in two connected studies that indicated that 3′,5′‐cyclic GMP and, to a lesser extent, 3′,5′‐cyclic AMP afford short oligomers in water. More recent studies in this area are discussed below.…”

“…Attention was mostly devoted to the 2',3'-cyclic form [21] both for direct polymerization and for the formation of phosphodiester bonds connectingp reformed oligonucleotides. [22] These studies weren ot developed further,a nd 3',5'-cyclic purine nucleotides were analyzed only in two connected studies [23,24] that indicated that 3',5'-cyclic GMP and, to al esser extent,3 ',5'-cyclic AMP [23] afford short oligomers in water.M ore recent studies [25,26,27] in this area are discussed below.…”