Aubrey R. Hill

The limits of template-directed synthesis with nucleoside-5′-phosphoro(2-methyl)imidazolides

In earlier work we have shown that C-rich templates containing isolated A, T or G residues and short oligo(G) sequences can be copied effectively using nucleoside-5′-phosphoro(2-methyl)imida-zolides as substrates. We now show that isolated A or T residues within an oligo(G) sequence are a complete block to copying and that an isolated C residue is copied inefficiently.Replication is possible only if there are two complementary oligonucleotides each of which acts as a template to facilitate the synthesis of the other. We emphasize the severity of the problems that need to be overcome to make possible non-enzymatic replication in homogeneous aqueous solution. We conclude that an efficient catalyst Was involved in the origin of polynucleotide replication.

Synthesis of adenine from HCN tetramer and ammonium formate.

Adenine is formed in about 18% yield whenHCN tetramer is heated with ammonium formate at 110 °C. Theprebiotic significance of this reaction is discussed.

Cyclization of nucleotide analogues as an obstacle to polymerization

SummaryCyclization of activated nucleotide analogues by intramolecular phosphodiester-bond formation is likely to compete very effectively with template-directed condensation except in the cases of ribo- and arabinonucleotides. This could have excluded derivatives of most sugars from growing polyribonucleotide chains and thus reduced chain-termination in prebiotic polynucleotide synthesis.

Oligomerization of negatively-charged amino acids by carbonyldiimidazole

The carbonyldiimidazole-induced oligomerizations of aspartic acid, glutamic acid and O-phospho-serine are amongst the most efficient reported syntheses of biopolymers in aqueous solution. The dependence of the yields of products on the concentrations of reagents, the temperature and the enantiomeric composition of the substrate amino acids are reported. Catalysis by metal ions, particularly by Mg2+, is described. These reactions do not generate significant amounts of material in the size-range of several tens of residues that are thought to be needed for a polymer to function as a genetic material.

Catalysis of the Oligomerization of O-Phospho-Serine, Aspartic Acid, or Glutamic Acid by Cationic Micelles

Treatment of relatively concentrated aqueous solutions of O-phospho-serine (50 mM), aspartic acid (100 mM) or glutamic acid (100 mM) with carbonyldiimidazole leads to the formation of an activated intermediate that oligomerizes efficiently. When the concentration of amino acid is reduced tenfold, few long oligomers can be detected. Positively-charged cetyltrimethyl ammonium bromide micelles concentrate the negatively-charged activated intermediates of the amino acids at their surfaces and catalyze efficient oligomerization even from dilute solutions.

Template-directed oligomerization of 3-isoadenosine 5'-phosphate.

SummaryTemplate-directed oligomerization of an activated derivative of 3-isoadenosine 5′-phosphate (piA) on polyuridylic acid [poly(U)] was studied. The reaction of ImpiA is more efficient than the corresponding reaction of ImpA, and produces 3′–5′-linked oligomers while the reaction of ImpA gives only 2′–5′-linked oligomers. The base pairing between piA and poly(U) in this system is probably of the Hoogsteen type (involving the 6-amino group and N7 of 3-isoadenosine) rather than of the Watson-Crick type.

Which 3-ribofuranosyl-substituted purine 5′-phosphates undergo template-directed oligomerization?

SummaryWe have studied the oligomerization reactions of the 2-methylimidazolide derivatives of 3-isoisoguanosine 5′-phosphate (2) and 3-isoxanthosine 5′-phosphate (5) in the presence of a variety of homopolynucleotide templates. In no case did we observe a substantial template-facilitated production of long oligomers. Polyuridylic acid directed the synthesis of low molecular-weight products from both monomers. Polycytidylic acid, polyadenylic acid, polyinosinic acid, and polyguanylic acid were ineffective as templates in the systems that we investigated.