Ribose synthesis, prebiotic

Prebiotic ribose synthesis a critical analysis. Orig. Life Evol. Biosph., 18, 71-85. 

Shapiro, R. 1988. Prebiotic ribose synthesis. A critical analysis. Origins life Evol. Biosph. 18 71-85. 

R. Shapiro. Prebiotic ribose synthesis, a critical analysis. Origins of Life and Evolution of Biospheres, 18 (1988), 71-85. 

Any discussion of the prebiotic phosphorylation of nucleosides must take into account the probably neutral or alkaline conditions in a prebiotic environment. Some model phosphorylating systems have been studied, for example, the synthesis of /S-o-ribofuranose 1-phosphate from ribose and inorganic phosphate in the presence of cyanogen. Sodium trimetaphosphate will phosphorylate cw-glycols in good yield under alkaline... 

Two points thus argue against the participation of ribose in nucleic acid formation the lability of the molecule and the problems with its synthesis (the concentrations of the starting materials are too high). Other, newer and more effective syntheses seem necessary, whereby prebiotic conditions (although these are not known precisely) strongly limit the possibilities. 

Moderately simple syntheses have been performed for the purines cytosine and uracil but nothing seems to work as a prebiotic synthesis of the pyrimidines. Then adding the sugar ribose to the base makes them nucleosides and one phosphoric acid residue makes it a nucleotide, or specifically a mononucleotide a rare but curiously important sequence of events in present-day life but perhaps not for prebiotic chemistry and early life forms. 

Hydrogen cyanide and methanal are especially reasonable starting materials for the prebiotic synthesis of amino acids, purine and pyrimidine bases, ribose and other sugars. Formation of glycine, for example, could have occurred by a Strecker synthesis (Section 25-6), whereby ammonia adds to methanal in the... 

Formamide is itself hydrolyzed by water, meaning that it persists only in a relatively dry environment, such as a desert. Desert environments recently proposed as being potential sites for the prebiotic synthesis of ribose18 may hold formamide as well. Since formamide boils at —400 K, a mixture of formamide and water, if placed in the desert, would lose its water over time and end up as a pool of formamide. Within this pool, many syntheses are thermodynamically favorable polypeptides from amino acids, nucleosides from sugars and bases, nucleotides from nucleosides and inorganic phosphate, and RNA from nucleotides. Indeed, phosphate esters are also spontaneously synthesized. This includes ATP (from ADP and inorganic phosphate), nucleosides (from ribose borates and nucleobases), peptides (from amino acids), and others.19-21... 

First, the question of where nucleotide monomers may have come from is critical. Given that the formose reaction is the most likely candidate for the synthesis of prebiotic ribose, but yields very little pure material, the role of stereoselective catalysts (clays, amino acids, or lipid aggregates) in directing the reaction should be fully explored. In this respect, Wachters-hauser16 has advanced a scheme for nucleotide synthesis based on pyrite catalysis than can be readily tested. 

Proline is a stable, nontoxic, cyclic, secondary pyrrolidine-based amino acid with an increased pK value. Thus, proline is a chiral bidentate compound that can form catalytically active metal complexes (Melchiorre et al. 2008). Bidentate means that proline has not only one tooth but also a second one to bite and react. The greatest difference to other amino acids is a Lewis-base type catalysis that facilitates iminium and enamine-based reactions. It is especially noteworthy that cross-aldol condensations of unprotected glycoladehyde and racemic glyceralde-hyde in the presence of catalytic amounts of the Zn-(proline)2 gave a mixture of pentoses and hexoses (Kofoed et al. 2004). Again, proline seems to play the decisive role. The conditions are prebiotic the reaction proceeded in water for seven days at room temperature. It is remarkable that the pentose products contained ribose (34%), lyxose (32%), arabinose (21%), and xylose (12%) and that all are stable under the conditions. Thus, the diastereomeric and enantiomeric selection observed support the idea that amino acids have been the source of chirality for prebiotic sugar synthesis. 

The RNA world scenario has been developed to a greater extent than most of the other approaches to the origin of the first life. This does not mean it is correct but rather that the positive and negative aspects of this scenario are more clearly defined. Problems with this approach start with the absence of a plausible prebiotic synthesis of nucleosides from the RNA bases and ribose. After the nucleoside formation issues are solved, there is no obvious route to the activated monomers that are required for the formation of oligomers. Since the activated monomers undergo relatively rapid hydrolysis in aqueous solution, their rates of synthesis would have had to be faster than their rates of hydrolysis. Other unaddressed problems include formation of RNAs that catalyze the replication of other RNAs, and the catalysis of the ligation of these same RNA oligomers. 

There are a number of possible ways to stabilize sugars the most interesting one is to attach the sugar to a purine or pyrimidine, i.e., by converting the carbohydrate to a glycoside, but the synthesis of nucleosides is difficult under plausible prebiotic conditions. It has therefore been suggested that ribonucleotides could not have been the first components of prebiotic informational macromolecules (59). This has led to propositions of a number of possible substitutes for ribose in nucleic acid analogues, in what has been dubbed the "pie-RNA World" (60). 

The synthesis of RNA in extant biology, however, still relies upon the participation of proteins. The protein-fiTee de novo synthesis of RNA in a prebiotic reaction has yet to be demonstrated after several decades of effort (5). Many researchers have therefore concluded that RNA was not the first informational polymer of life. Rather, RNA was preceded by an RNA-Me polymer, or several generations of polymers, termed proto-RNAs, that were stracturally and functionally similar to RNA, but easier to assemble. Proto-RNA could have been comprised of different bases, sugars, and hnking molecules that were assembled through more thermodynamically and kinetically accessible pathways. Without the constraints of the current four RNA bases, ribose, and phosphate for the construction of an informational polymer, the possible composition of proto-RNAs seems limitless. However, tte existence of putative monomer units in the prebiotic chemical inventory for the assembly of proto-RNA would have been dictated by astro- and geochemical processes, paring down the set of molecules from which nature could select. 

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