Nucleosides prebiotic

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 ... 

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. 

One of the more difficult prebiotic syntheses is that of the nucleosides. Heating of ribose and purines at 100°C gives fair yields (2-20%) of a mixture of isomers of the purine ribosides, with some of the correct 13-isomer being produced.45 However, a mixture of pyrimidines and ribose gives no detectable yield of nucleosides. Whether the inability to synthesize pyrimidine ribosides is a matter of not trying the correct conditions or whether pyrimidine nucleosides were not involved in the first organisms remains to be determined. 

Urea is another prebiotic condensing agent for the phosphorylation of nucleosides. Condensed phosphates have been obtained from ammonium phosphate and urea [126], while alcohols are easily phosphorylated at 150 °C by urea and phosphoric acid [127]. When an equimolar mixture of uridine 48 and Na2HP04 was heated at 100 °C in the presence of a ten-fold molar excess of urea and ammonium chloride, 97% of the phosphate was found to be incorporated into the nucleoside moiety mainly as uridine 5 -monophosphate 49 and uridine 2, 3 - cyclic phosphate 50 (Scheme 23). 

Phosphorus is abundant on Earth, both as an element (the llth-most abundant atom in Earth s crust) and as phosphate. Meteorites hold a variety of phosphate-containing minerals and some phosphide minerals.10 Scientists at the University of Arizona have recently suggested that Fe3P, the mineral schreibersite, leads to the formation of phosphate and phosphite when corroded in water. Although phosphorylation of alcohols was not demonstrated, mechanistic considerations suggest that it should be possible. It is noteworthy that a clear prebiotic pathway for the chemical incorporation of phosphate into RNA or DNA has not been found. No nucleosides (nucleobases joined to sugars) have been reported from meteorites. Nor has evidence been found in any meteorite of the presence of nucleosides or nucleotides (nucleosides attached to phosphates). That suggests that nucleic acids were first formed as products of metabolism. 

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... 

Schoffstall, A.M. 1976. Prebiotic phosphorylation of nucleosides in formamide. Origins Life Evol. Biosph. 7 399-412. 

Although there are a number of inefficient steps in most proposed prebiotic syntheses of ribotides, the major objection to RNA as the primogenitor of life has been the relatively small yield of ribose in the formose reaction, a simple condensation of glycoaldehyde. Muller et a/.,18 however, have discovered a variation of the formose reaction that produces a limited mix of pentose diphosphates in which the ribose forms predominate (52 14 23 11, ribose arabinose lyxose xylose). Although many critical chemical roadblocks remain (such as the extremely low yield of pyrimidine nucleosides following the condensation of ribose and free bases), this advance belies the previously held view that products of the formose reaction are necessarily so chemically diverse that they are the carbohydrate analog of petroleum. 19... 

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. 

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. 

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