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In the latter half of the 1950s, the author had the good fortune to be accepted by Francis Crick as an observer of, and occasional verbal contributor to, their efforts to understand DNA replication, protein synthesis, and other aspects of classical molecular biology. The author has had the opportunity to observe his mind at work in Cambridge, England, and later at the Salk Institute, where he served in an advisory capacity until 1977, and then as a faculty member until his death. A list favorite papers that Crick authored or coauthored would include those on diffraction by a helix, coiled-coils, the adaptor hypothesis, wobble pairing, the three-letter code, the structure of collagen, the prediction of an "RNA world" and the two short papers on the structure of DNA that launched many thousands of manuscripts.

Focuses on the discovery of the adenosine triphosphate (ATP) synthase process by Dr. Peter Mitchell. Experiences of the author in a meeting with Mitchell; Why his idea of cells generating energy with proton pumps seemed ridiculous at the time; Observation that his work required a paradigm shift in the field of molecular biology.

Discusses the deoxyribonucleic acid (DNA) chemical ability to act as templates for the synthesis of peptide nucleic acid (PNA). Determination of the efficiency of ligation; Proceedings involved with the ligation forming the chimeras; Reference to the chemical factors associated with the synthesis of PNA.

Several classes of nucleic add 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 adds (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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.

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.

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.

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.

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.