Nucleosides, prebiotic synthesis

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. 

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... 

Sanchez RA, Orgel LE. Studies in prebiotic synthesis. V. Synthesis and photoanomerization of pyrimidine nucleosides. J. Mol. 91. Biol. 1970 47 531-543. 

Powner MW, Anastasi C, Crowe MA, Parkes AL, Raftery J, Sutherland ID. On the prebiotic synthesis of ribonucleotides photoanomerisation of cytosine nucleosides and nucleotides re- 94. visited. ChemBioChem. 2007 8 1170-1179. 

A major problem with the RNA world scenario is the absence of a convincing prebiotic synthesis of nucleosides (Figure 1). Dry heating of a... 

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. 

So far, all the prime constituents of nucleic acid synthesis have proved surprisingly easy to prepare by prebiotic synthesis. What has proved difficult has been the synthesis of nucleosides (organic bases and sugars... 

Since pentoses and phosphates were not included in the HCN-NH4OH mixtures one could not expect the formation of nucleosides or nucleoside phosphates in such mixtures, as in the biochemical de novo synthesis of purine nucleotides, even though an adenine derivative of possible nucleosidic nature was detected in one of our early experiments. Alternate biochemical routes also exist (salvage pathways) for the synthesis of nucleosides from the preformed bases. The latter general approach has been followed in the prebiotic synthesis of purine nucleosides, and the former has been used in the synthesis of pyrimidine nucleosides and nucleotides. 

Fuller, W. D., Sanchez R. A. and Orgel L. E. (1972) Studies in prebiotic synthesis. Solid-state synthesis of purine nucleosides. J. Molec. Evolution 1, 249-257. 

More exotic alternatives to nucleosides have been proposed based on the peptide nucleic acid (PNA) analogues of Nielsen and coworkers (93). Miller and coworkers (94) were able to demonstrate the facile prebiotic synthesis of all of the components of PNA under the same chemical conditions required for the synthesis of the purines or pyrimidines. Nevertheless there are maity alternative structures, which have not yet been investigated. 

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... 

Although the results of all experiments so far carried out on nucleoside synthesis under prebiotic conditions have been disappointing, the next step, to give the nucleotides, has been carried out using nucleosides synthesized in today s laboratories. There are two preconditions for nucleotide syntheses ... 

The RNA world hypothesis caused prebiotic phosphate chemistry to become an attractive research area again unfortunately, no clear evidence for a realistic nucleotide synthesis under the simplified conditions of a primitive Earth has yet appeared. Important work on nucleoside phosphorylation has, however, been done. It is important to distinguish between ... 

Nowadays, activities of nucleic acids are controlled by interactions of Mg, Ca or Zn, but also by heavy-metal ions or electrophilic agents with certain specific sequences (e.g. in induction of metallothionein). Though this does imply NAs to act as ligands in physiological conditions, it need not imply that they could achieve the above sequence of steps, let alone the problem that up to now not even a hint of a prebiotic NA synthesis pathway was demonstrated, not even when using polyphosphoric acid in organic solvents. The E (L) values for NAs, nucleoside triphosphates or simpler species such as glycerinaldehyde-2,3-diphosphate are way too low to permit the sequence of events on their own. 

Ponnamperuma C, Mack R. Nucleotide Synthesis under Possible Primitive Earth Conditions. Science 1965 48 1221-1223. Lohrmann R, Orgel LE. Urea-inorganic phosphate mixtures as prebiotic phosphorylating agents. Science 1971 171 490-494. Reimann R, Zubay G. Nucleoside phosphorylation a feasible step in the prebiotic pathway to RNA. Orig. Life Evol. Biosph. 1999 29 229-247. 

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). 

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