Self-assembling sequence-adaptive peptide nucleic acids.

Several classes of nucleic acid analogs have been reported, but no synthetic informational polymer has yet proven responsive to selection pressures under enzyme-free conditions. Here, we introduce an oligomer family that efficiently self-assembles by means of reversible covalent anchoring of nucleobase recognition units onto simple oligo-dipeptide backbones [thioester peptide nucleic acids (tPNAs)] and undergoes dynamic sequence modification in response to changing templates in solution. The oligomers specifically self-pair with complementary tPNA strands and cross-pair with RNA and DNA in Watson-Crick fashion. Thus, tPNA combines base-pairing interactions with the side-chain functionalities of typical peptides and proteins. These characteristics might prove advantageous for the design or selection of catalytic constructs or biomaterials that are capable of dynamic sequence repair and adaptation.

Protein disulfide oxidoreductases and the evolution of thermophily: was the last common ancestor a heat-loving microbe?

Protein disulfide oxidoreductases (PDOs) are redox enzymes that catalyze dithiol-disulfide exchange reactions. Their sequences and structure reveal the presence of two thioredoxin fold units, each of which is endowed with a catalytic site CXXC motif. PDOs are the outcome of an ancient gene duplication event. They have been described in a number of thermophilic and hyperthermophilic species, where they play a critical role in the structural stabilization of intracellular proteins. PDOs are homologous to both the N-terminal domain of the bacterial alkyl hydroperoxide reductase (AhpF) and to the eukaryotic protein disulfide isomerase (PDI). Phylogenetic analysis of PDOs suggests that they first evolved in the crenarchaeota, spreading from them into the Bacteria via the euryarchaeota. These results imply that the last common ancestor (LCA) of all extant living beings lacked a PDO and argue, albeit weakly, against a thermophilic LCA.

Amino acid dependent formation of phosphate anhydrides in water mediated by carbonyl sulfide.

Carbonyl sulfide (COS), a component of volcanic gas emissions and interstellar gas clouds, is shown to be an efficient condensing agent in the context of phosphate chemistry in aqueous solutions. We report that high-energy aminoacyl-phosphate anhydrides and aminoacyl adenylates are generated in solutions containing amino acids, COS, and the corresponding phosphate molecule. We further show that the mixed anhydrides of amino acids and inorganic phosphate are phosphorylating agents, producing pyrophosphate in better than 30% yield in the presence of Ca2+ precipitates. The amino acid dependent activations of phosphate reported here, which occur in parallel with the production of peptides, suggest that these two reactions may have shared a common intermediate on the prebiotic Earth.

Prebiotic adenine revisited: eutectics and photochemistry.

Recent studies support an earlier suggestion that, if adenine was formed prebiotically on the primitive earth, eutectic freezing of hydrogen cyanide solutions is likely to have been important. Here we revisit the suggestion that the synthesis of adenine may have involved the photochemical conversion of the tetramer of hydrogen cyanide in eutectic solution to 4-amino-5-cyano-imidazole. This would make possible a reaction sequence that does not require the presence of free ammonia. It is further suggested that the reaction of cyanoacetylene with cyanate in eutectic solution to give cytosine might have proceeded in parallel with adenine synthesis.

Prebiotic chemistry and the origin of the RNA world.

The demonstration that ribosomal peptide synthesis is a ribozyme-catalyzed reaction makes it almost certain that there was once an RNA World. The central problem for origin-of-life studies, therefore, is to understand how a protein-free RNA World became established on the primitive Earth. We first review the literature on the prebiotic synthesis of the nucleotides, the nonenzymatic synthesis and copying of polynucleotides, and the selection of ribozyme catalysts of a kind that might have facilitated polynucleotide replication. This leads to a brief outline of the Molecular Biologists' Dream, an optimistic scenario for the origin of the RNA World. In the second part of the review we point out the many unresolved problems presented by the Molecular Biologists' Dream. This in turn leads to a discussion of genetic systems simpler than RNA that might have "invented" RNA. Finally, we review studies of prebiotic membrane formation.

Some consequences of the RNA world hypothesis.

It is now generally accepted that our familiar biological world was preceded by an RNA world in which ribosome-catalyzed, nucleic-acid coded protein synthesis played no part. If the RNA world was the first biological world there is little that one can learn from biochemistry about prebiotic chemistry, except that the formation and polymerization of nucleotides were once prebiotic processes. If the RNA world was not the first biological world, the above conclusion may not be justified, and one can speculate that the monomers of earlier genetic polymers might be recognizable as important biochemicals. This suggests that the construction of replicating polymers from simple, not necessarily standard, aminoacids should be explored.

Thiol-mediated degradation of DNA adsorbed on a colloidal gold surface.

When [32P]-labeled DNA is adsorbed on colloidal gold from a 130mmol dm-3 solution of KH2PO4, it can subsequently be eluted with cold DNA without undergoing detectable degradation. Similarly, DNA can be incubated in solution in the presence or absence of colloidal gold with high concentrations of ß-mercaptoethanol or hexane-1-thiol without significant degradation. However, when adsorbed DNA is eluted from gold with solutions of one of the thiols, it is recovered as a mixture of mononucleotides and short oligomers. The extent of degradation increases with increasing concentration of the thiol and with increasing elution temperature. Our results emphasize that in designing protocols involving DNA adsorbed on gold surfaces, it is important to avoid allowing the DNA to come into contact with even moderate concentrations of thiols.

Is cyanoacetylene prebiotic?

Cyanoacetylene is an earlier intermediate in a proposed prebiotic synthesis of cytosine, while cyanoacetaldehyde is a later intermediate. There is no scientific basis for the claim that cyanoacetaldehyde is more plausibly prebiotic than cyanoacetylene in this context.

Synthesis of adenine from HCN tetramer and ammonium formate.

Adenine is formed in about 18% yield when HCN tetramer is heated with ammonium formate at 110 degrees C. The prebiotic significance of this reaction is discussed.