Origin of Informational Polymers

Abstract

We have measured the stabilities of the bonds that are critical for determining the half-life of ribonucleotides and the ␤-glycosidic and 3-and 5-phosphoester bonds. Stabilities were measured under a wide range of temperatures and water/formamide ratios. The stability of phosphodiester bonds in oligoribonucleotides was determined in the same environments. The comparison of bond stabilities in the monomer versus the polymer forms of the ribo compounds revealed that physico-chemical conditions exist in which polymerization is thermodynamically favored. These conditions were compared with those determining a similar behavior for 2-deoxyribonucleosides, deoxyribonucleotides, and deoxyribooligonucleotides and were shown to profoundly differ. The implications of these facts on the origin of informational polymers are discussed.Minimal requirements for informational polymers to have originated under prebiotic conditions are a unitary chemical frame for the synthesis of nucleobases and a favorable thermodynamic energy balance for the polymerization of nucleotides to oligonucleotides.A Formamide-based Unitary Chemistry-To gather into a single reaction milieu all the precursors necessary for the assembly of the first informational polymers, a unitary chemical frame is needed. A series of observations suggest that formamide (NH 2 CHO) chemistry might have provided such a frame.To summarize the evidence: the one-carbon compound formamide is a highly versatile building block for the syntheses of all the necessary precursor nucleic bases. We have reported (Refs. 1-4 and references therein) the synthesis of purine, N 9 -formylpurine, adenine, N 9 , N6-diformyladenine, hypoxanthine, cytosine, hydroxypyrimidine, 4(3H)-pyrimidinone, uracil, 5,6-dihydrouracil, thymine, 5-hydroxymethyluracil, AICA (5-aminoimidazole-4-carboxamide), FAICA (5-formylaminoimidazole-4-carboxamide), and urea. These compounds are obtained from formamide heated in the presence of simple inorganic catalysts such as silica, alumina, zeolites, CaCO 3 , TiO 2 , common clays, kaolin, montmorillonites, olivines, and cosmic dust analogues of olivines. In all cases and for each catalyst several compounds were simultaneously formed, as summarized in Ref. 4.The richest yields were obtained in the presence of clays, TiO 2 , and cosmic dust analogues. Guanine is conspicuously absent, but a possible efficient substitute in base pairing might have been provided by hypoxanthine. Notably, formamide also yields purine acyclonucleosides through a formose-like condensation of N-formyl derivatives (2), providing a solution to the long-standing problem of the lack of reactivity between nucleobases and ribose or 2Ј-deoxyribose. In addition, formamide is an efficient activator of nucleoside transphosphorylation (Refs. 5-7), 2 further supporting its possible relevance in the prebiotic polymerization reactions that did lead to pregenetic informational macromolecules.Formamide is easily formed by hydrolysis of HCN and is stable in liquid form over a wide range of temperatures (2.5-2...

Nucleoside Phosphorylation by Phosphate Minerals

“…The kinetics of nucleotide dephosphorylation in these conditions is reported in Ref. (15) and is in full kinetic agreement. The half-lives of the components of the reaction and of its products in formamide at 90°C were separately measured by HPLC (data not shown) and were (min): adenine Ͼ 10 5 , 5Ј-AMP 1.10 ϫ 10 3 ; 3Ј-AMP 0.40 ϫ 10 3 ; 2Ј-AMP 0.21 ϫ 10 3 ; 2Ј:3Ј-cyclic AMP 7.0 ϫ 10 4 .…”

“…In water no phosphorylated forms were observed (data not shown), and the only reaction that took place was the cleavage of the ␤-glycosidic bond and the consequent release of adenine. As reported (15), the half-life of this bond at 90°C in water is 4.5 ϫ 10 2 h. Fig. 1A shows the formation of different nucleotides in KH 2 PO 4 -containing formamide.…”

“…The 10-fold protective effect on the ␤-glycosidic bond exerted by the presence of a phosphate moiety bound at 5Ј was reported (15). Thus, adenine is mostly formed from unreacted, unphosphorylated adenosine.…”

Generation of Long RNA Chains in Water

“…11. In brief, terminally labeled RNA oligonucleotides were hydrolyzed in water at 90°C for different time periods (between 0 and 24 h) and pre-analyzed on polyacrylamide gel.…”

Chemical and biological effects of substitution of the 2-position of ring-expanded (‘fat’) nucleosides containing the imidazo[4,5-e][1,3]diazepine-4,8-dione ring system: The role of electronic and steric factors on glycosidic bond stability and anti-HCV activity

“…As it is well known that glycosidic bonds in 2′-deoxynucleosides/-tides (DNA) are nearly two orders of magnitude less stable than their ribose counterparts (RNA), 16 our best hope for preparing the target 2-substituted 5:7-fused nucleoside analogues was to replace their 2′-deoxyribose moiety with a ribosyl sugar at position-1. Besides, since the target Flaviviridae are RNA viruses, synthesis of ribose nucleoside analogues as potential inhibitors would only be logical, notwithstanding the potent in vitro anti-HCV/WNV activities of a few 2′-deoxyribose analogues of RENs.…”